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Cancer Compass: Advances, Approval and Regulatory Updates

New therapies for advanced cancers are focusing on precision medicine for underserved subpopulations, with promising treatments like antibody-drug conjugates and radioligand therapies gaining traction in clinical trials. The Oncology Compass report highlights the growing oncology market, fueled by increased spending. It covers FDA and EMA approvals of breakthrough therapies, M&A trends, and the transformative role of Generative AI in improving diagnostics, early detection, and personalized treatments.

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Cancer Compass: Advances, Approval and Regulatory Updates

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  1. December, 2024 Cancer Compass Advances, Approval and Regulatory Updates (Q4 2023-Q3 2024)

  2. TABLE OF CONTENTS 01. ONCOLOGY LANDSCAPE 04 This section examines the overall oncology landscape, focusing on global oncology spending, top-performing drugs, changes in total drug sales compared to previous years, and indications for approval in the US, EMA, and APAC, along with key highlights. Additionally, it will analyze mergers and acquisitions, total deal counts in the oncology market, and the leading companies involved 02. KEY APPROVALS 22 This section reviews recent oncology drug approvals by the EMA and FDA, highlighting drugs with unique designations and their indications. It also covers newly endorsed tools and devices, as well as the emergence of AI/ML tools, including CE-certified & FDA options 03. RESEARCH & DEVELOPMENT 40 This section investigates ongoing clinical trials from Q4 2023 to Q3 2024, highlighting major indications and their corresponding phases. It also examines developments in the breakthrough therapy market, notable approvals, and PRIME acknowledged by the EMA breakthrough designations 04. FUTURE TRENDS 45 This section examines breakthroughs in Antibody-Drug Conjugates (ADCs) and the evolving landscape of Bispecific antibodies, along with advancements in Radioligand therapies

  3. Cancer Compass Advances, Approval & Regulatory Updates OVERVIEW New therapies for advanced cancers are being developed, focusing on precision medicine for underserved patient subpopulations. Promising novel treatments, such as antibody-drug conjugates and Radioligand are increasingly featured in clinical trials. The success rate for oncology clinical development reached 12% in 2024 compared to 10% in 2023, aided by improved productivity and reduced trial complexity. Overall, advancements in oncology research are being driven by regulatory initiatives and the integration of artificial intelligence This report provides a detailed global perspective on oncology, covering leading medications for various diseases, year-over-year spending comparisons, recent breakthroughs in clinical trials, significant mergers and acquisitions, regulatory updates, and innovative discoveries Proportion of the pipeline in development for cancer, 2020—24 (%) 40.1 39.8 39 37.5 36.7 2020 2021 2022 2023 2024 Sources- IQVIA , Pharma R&D Page 3

  4. Cancer Compass Advances, Approval & Regulatory Updates SUMMARY KEYTRUDA is the highest-selling oncology drug, generating USD 27B in revenue. Its success stems from an effective expansion strategy and a broader range of approved indications In February 2024, AbbVie acquired Immunogen for USD 10.1B, marking it as a significant deal of the year Largest collaboration deal is between Daiichi Sankyo and Merck, valued at USD 22B for the development of antibody-drug conjugates (ADCs) Other top-selling drugs include DARZALEX (USD 10.7B), OPDIVO (USD 9.2B), PERJETA (USD 6.8B), AND TECENTRIQ (USD 6.5B) Approximately 36.3% of collaborations are focused on ADCs, indicating their growing importance in oncology IMFINZI (AstraZeneca) has also made it to the top 10, achieving impressive sales of USD 4.4B, reflecting a 47.7% increase compared to the previous year AI-focused partnerships remain a critical area of interest, primarily aimed at enhancing the discovery and development of cancer drugs.- About 55% of mergers and acquisitions are valued at over USD 2B Drugs like PERJETA AND IMBRANCE, which have not received any new indications during our analysis period, are showing negative growth in sales Mergers and acquisitions are occurring to strengthen a company's position within its industry, enhance flagship products, diversify pipelines, and expand drug portfolios Page 4

  5. Cancer Compass Advances, Approval & Regulatory Updates ONCOLOGY REVIEW Global Oncology Spending (USD B) 223 14.4% 255 2023 2024 (F) Increasing acceptance of biosimilars and generics is one of the factors driving the rise in overall spending. FDA has approved 2 generic medications and 6 biosimilar in H1 2024 Cost of novel cancer drugs are increasing. One of the reason is the launch of new therapies like CAR-T, ADCs and bi/multi-specific antibodies. Novel cancer drug cost with more than USD 100,000 represents 85% of the launches Top Oncology Drugs H2 2023 – H1 2024 (USD B) Sales Growth KEYTRUDA +37.7% 27.0 Immunotherapy has seen significant advancements in the H1 2024, including the approval of the first bispecific T-cell engager for a solid cancer type, an early-stage indication for another bispecific T-cell engager, a new class of immunotherapy for bladder cancer, two new indications for CAR T-cell therapy, and new indications for immune checkpoint inhibitors DARZALEX +38% 10.7 OPDIVO 9.2 +11.9% PERJETA 6.8 -24.7% 6.5 TECENTRIQ - 5.5% 6.1 TAGRISSO Spending on PD-1/PD-L1 inhibitors, which are frequently used to treat solid tumors, is expected reach to USD 59.4B in 2024 +14.3% REVLIMID 6 - 41.4% Mature markets like US, EU, China is expected to be major countries in terms of spending in 2024 5.4 XTANDI +44.1% IBRANCE 4.4 -15.9% IMFINZI 4.4 +47.7% Page 5

  6. Cancer Compass Advances, Approval & Regulatory Updates 1) USD 27B +37.7% Sales Growth Global Sales KEYTRUDA first approved by the FDA in 2014, is a type of immunotherapy used to treat melanoma, non- small cell lung cancer (NSCLC), hodgkin lymphoma, head & neck squamous cell carcinomas, urothelial carcinoma, microsatellite instability-high or deficient mismatch repair, and GEJ adenocarcinoma It is the first FDA-approved tissue-based broad CDx that is validated for all solid tumors INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC Combination with carboplatin & paclitaxel for adult patients with primary advanced or recurrent endometrial carcinoma In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma In combination with chemoradiotherapy for the treatment of patients with International Federation of Gynecology and Obstetrics 2014 Stage III-IVA cervical cancer Combination with gemcitabine and cisplatin, for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer Key Highlights Sales increased in Q2 2024 by 16% due to global uptake in earlier stage indications, including triple-negative breast cancer & renal carcinoma as well as NSCLC in the US 2) USD 10.7B Global Sales +36% Sales Growth Daratumumab under the brand name DARZALEX, is used to treat adults with multiple myeloma and light chain amyloidosis Drug received conditional marketing authorization from EMA in 2016 which was switched to full marketing authorization in 2018 INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC Combination with Bortezomib, Lenalidomide, and Dexamethasone for induction and consolidation in patients eligible for autologous stem cell transplant Key Highlights DARZALEX is the leading revenue-generating drug for the company with 16.3% sales growth in Q2 2024 due to Strong FASPRO adoption and share gains across all areas Sources- Drugs.com, DARZALEX Page 6

  7. Cancer Compass Advances, Approval & Regulatory Updates 3) USD 9.2B Global Sales +11.9% Sales Growth Prescription medicine used to treat head & neck, urothelial carcinoma, MSI-H or dMMR metastatic colorectal cancer, renal cell carcinoma, melanoma, NSCLC, and hodgkin lymphoma OPDIVO was first approved in 2014 by the FDA for the treatment of patients with unresectable or metastatic melanoma It has been highlighted for its advantage over its rival KEYTRUDA, in terms of not requiring biomarker testing INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC Treatment of resectable NSCLC and unknown EGFR mutations or ALK rearrangements, for neoadjuvant treatment, in combination with platinum- doublet chemotherapy, followed by single-agent OPDIVO as adjuvant treatment after surgery Combination with cisplatin and gemcitabine, for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma Treatment of adult and pediatric patients 12 years and older with completely resected stage IIB or IIC melanoma Key Highlights Sales increased by 15% in Q2 2024 in the US & 6% in the international market due to higher demand as a result of launches for new indications and core indications 4) -24.7% Sales Growth USD 6.8B Global Sales PERJETA is indicated for use in combination with trastuzumab and docetaxel for the neoadjuvant treatment of patients with HER2-positive, locally advanced metastatic breast cancer PERJETA was first approved in 2017 by FDA & in 2013 by EMA INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC NO INDICATIONS APPROVED Key Highlights Sales in the US decreased by 7% due to a change in reserves associated with US government plans, offsetting growth in the international market (China & Brazil) In Europe, sales of PERJETA lowered by -16% in Q2 2024 mainly due to the launch of Phesgo NSCLC- Non-small lung cancer cell, EGFR- Epidermal growth factor receptor, ALK- Anaplastic lymphoma kinase, HL- Hodgkin Lymphoma, HNSC- Head & Neck squamous cell carcinoma, GEJ- Gastroesophageal junction, CDx - companion Diagnostic, MM- Multiple myeloma, RCC- Renal cell carcinoma, MSI-H- microsatellite instability-high, dMMR- deficient Mismatch repair, mCRC – metastatic colorectal cancer Sources- Reuters, Merck, FDA, Market expansion, OPDIVO Page 7

  8. Cancer Compass Advances, Approval & Regulatory Updates 5) USD 6.5B Global Sales -5.5% Sales Growth TECENTRIQ is a type of cancer immunotherapy known as a PD-L1 inhibitor that helps the immune system recognize and attack cancer cells Approved by the FDA, it is indicated for the first-line treatment of adult patients with metastatic lung cancer including small- cell, hepatocellular, urothelial carcinoma, and metastatic melanoma INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC # Anti-PD-L1 cancer immunotherapy injection for multiple cancer type #TECENTRIQ Hybreza (atezolizumab and hyaluronidase-tqjs) Key Highlights In the US, sales fell by 8% in Q2 2024, primarily due to ongoing competition in the HCC and NSCLC cell indications In Japan, sales decreased by 2% in Q2 2024 because of a slowdown in market penetration within a competitive environment 6) USD 6.1B Global Sales +14.3% Sales Growth Oral drug is indicated for adult patients with locally advanced or metastatic NSCLC that has specific mutations in the EGRF, including T790M mutation-positive NSCLC Approved for the treatment in more than 90 countries, it was first approved by the FDA for NSCLC in 2020 INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC Unresectable, Stage III EGFR-mutated NSCLC Key Highlights Sales increased by 7.8% in Q2 2024 due to growth in 1st-line setting and increasing adjuvant demand NSCLC- Non-small lung cancer cell, RCC- Renal cell carcinoma, EGFR- Epidermal growth factor receptor, HCC- Hepatocellular carcinoma, SCLC- Small cell Lung cancer, PD-L1- Programmed Death –Ligand 1, EGFR-TKI as first-line treatment for EGFRm advanced NSCLC, EGFR-Mutated NSCLC trial Sources- FDA, FDA , BMS, ESMO, Patent loss, Roche 2022, Globewire, investor report , Brew, Healthcare Page 8

  9. Cancer Compass Advances, Approval & Regulatory Updates 7) USD 6B Global Sales -41.4% Sales Growth Thalidomide analog with the major indications including MM, myelodysplastic syndromes, and lymphoma Lenalidomide under the brand name REVLIMID by Celegene Corporation (Bristol Myers Squibb) , was first approved as the first-line therapy for the treatment of MM by the FDA in 2005 INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC NO INDICATIONS APPROVED Key Highlights Sales decreased 8% in Q2 2024 due to the entry of generic versions after its patent loss in 2022 8) USD 5.4B Global Sales +44.1% Sales Growth XTANDI becomes the first and only androgen receptor signaling inhibitor approved by the FDA for the treatment of patients with nmCRPC with biochemical recurrence at high risk for metastasis in 2023 INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC Nonmetastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis Key Highlights Sales increased by 22.4% in Q2 2024 due to the approval of additional indications for high-risk prostate cancer in both US and international markets NSCLC- Non-small lung cancer cell, nmCRPC- non-metastatic castration- sensitive prostate cancer, MM- Multiple Myeloma Sources- Astrazeneca, EMA, FDA , ESMO , Finance, Roche Page 9

  10. Cancer Compass Advances, Approval & Regulatory Updates 9) USD 4.4B Global Sales -15.9% Sales Growth Used to treat locally advanced or metastatic breast cancer Ibrance was approved by EMA in 2016. The drug was first approved by the FDA in 2015 under accelerated approval INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC NO INDICATIONS APPROVED Key Highlights Sales decreased by 8% in Q2 2024 due to lower global demand, increased competitive pressure, and a reduction in clinical trial purchases 10) USD 4.4B Global Sales +47.7% Sales Growth IMFINZI is used to treat types of NSCLC, ES- SCLC, bile ducts, gallbladder cancer, unresectable hepatocellular carcinoma, and advanced or recurrent dMMR endometrial cancer First approved in the US in 2017 INDICATION APPROVED IN Q4 2023 –Q3 2024 US EMA APAC Resectable early-stage (IIA-IIIB) NSCLC and no known EGFR mutations or ALK rearrangements. IMFINZI plus chemotherapy for mismatch repair deficient advanced or recurrent endometrial cancer In combination with carboplatin and paclitaxel is indicated for the first-line treatment of adults with primary advanced or recurrent endometrial cancer Key Highlights In the US, sales increased due to ongoing demand for new product launches related to biliary tract cancer and HCC In Europe, sales growth was driven by a larger market share in SCLC and expanded reimbursement options for biliary tract cancer, HCC, Stage IV NSCLC, and SCLC DMMR: deficient Mismatch Repair, NSCLC: Non- small cell lung cancer, ALK- Anaplastic lymphoma kinase, ES-SCLC: extensive-stage small cell lung cancer, GI: Gastrointestinal, HCC- Hepatocellular Cancer, SCLC: small cell lung cancer Sources- Astrazeneca, Astella, Pfizer , Precision Medicine Page 10

  11. Cancer Compass Advances, Approval & Regulatory Updates M&A AND COLLABORATION Q4 2023- Q3 2024 Pharma M&A deals in 2024 Collaboration in 2024 Oncology There have been 26 collaborations & partnerships related to oncology globally till October 2024. With ADC being the primary hotspot for deals, it represents a significant 36.3% 14 Others 43 Distribution of Notable Collaboration by Areas (Q4-2023 –Q3 2024) Data as of October 2024 In 2024, 57 pharma deals took place, out of which 14 were oncology-related,12 were acquisitions & 2 were Merger deals A significant number of mergers and acquisitions involve antibody-drug conjugates (ADC) and radioligands Almost all the companies acquired by the big pharma companies are small-size biotech companies. One of the reasons for such an acquisition can be to offset revenue losses because of patent expiration 3 Others ADC 2 Bi-specific Small molecule 2 4 Approximately 42.11% of significant collaborations are centered on leveraging AI to advance cancer drug discovery and enhance drug development Distribution of Notable Deals by Valuation (Q4-2023 –Q3 2024) Biggest Collaboration deal (Q4 2023-Q3 2024) 2 USD 22B 400-800M >2B 8 5 800 M-2B Biggest Acquisition deal (Q4 2023-Q3 2024) USD 10.1B Sources- Brew, Healthcare, Deloitte, Brew, Healthcare, Deloitte, citeline, Abbvie, Healthcaretech E&Y, Deals Page 11

  12. Cancer Compass Advances, Approval & Regulatory Updates ACQUIRER TARGET DEAL SIZE 01 USD 10.1B Abbvie will strengthen its oncology portfolio by adding ImmunoGen's ELAHERE ImmunoGen's ADC follow-on pipeline will expand AbbVie's solid tumor pipeline of next- generation immuno-oncology assets and novel targeted therapeutics ELAHERE is the first and only antibody-drug conjugate (ADC) approved by the FDA for ovarian cancer 02 USD 5.8B Deal will expand oncology portfolio by adding Lung cancer medication KRAZATI (adagrasib) Additionally,clinical resources such as a Phase 1 MTA-cooperative PRMT5 inhibitor and a KRAS program have two candidates in the Phase 1 stage of development will be acquired Adagrasib, sold under KRAZATI, is an anticancer medication used to treat NSCLC. Adagrasib is an inhibitor of G12C mutated KRAS 03 USD 2.9B Deal will support Novartis's efforts to develop next-generation cancer treatments Pelabresib (CPI-0610), a new therapy option with a well-tolerated safety profile for myelofibrosis in conjunction with JAKAVI (ruxolitinib) 04 USD 2.4B Deal will expand AstraZeneca’s portfolio to radio conjugates Will acquire Fusion pipeline of Radioconjugates, FPI-2265 FPI-2265 is under development for the treatment of metastatic hormone-refractory (castration-resistant, androgen-independent) prostate cancer NSCLC: Non-small cell lung cancer, KRAS: Kirsten rat sarcoma viral oncogene homologue GTPase Sources- Abbvie, Healthcaretech, Ono, Healthcaremea Page 12

  13. Cancer Compass Advances, Approval & Regulatory Updates ACQUIRER TARGET DEAL SIZE 05 USD 2.4B ONO will increase its oncology pipeline with immediate QINLOCK and possible Vimseltinib additions Ono will gain access to Deciphera’s macrophage colony-stimulating factor-1 receptor inhibitor vimseltinib, the unc-51-like autophagy activatingkinase inhibitor DCC-3116, and several other oncology candidates 06 USD 2B Johnson & Johnson will use Ambrx's exclusive ADC technology to design, develop, and market targeted oncology therapies through the acquisition This technology will combine highly specific-targeting monoclonal antibodies safely attached to a powerful chemotherapeutic payload 07 USD 1.8B Genmab will be able to expand its market share in gynecologic oncology and build a strong presence in solid tumors by including Rina-S in its portfolio Acquisition will grant Genmab global rights to three clinically developed candidates, including rinatabart sesutecan (Rina-S) Rinatabart sesutecan is a folate receptor alpha-targeted ADC for ovarian cancer. The agent is being evaluated in a phase 2 study 08 USD 1.3B Boehringer Ingelheim will expand its immuno-oncology pipeline with the addition of Nerio's novel PTPN2/N1 PTPN1/PTPN2 inhibitors have the potential to enhance T cell anti-tumor immunity ADC: Antibody-drug conjugate Sources- Pharmatech, Biopharmadive, Pharmaceutical world, Genmab, Novartis, BI, Biogen Page 13

  14. Cancer Compass Advances, Approval & Regulatory Updates ACQUIRER TARGET DEAL SIZE 09 USD 1.3B This deal will serve as an entry point for Eli Lily in radioligand medications for tumors Eli Lilly will receive clinical-stage medications from Acquiring Point, two of which could rival Novartis's authorized radiopharmaceuticals PNT2002,- for mCRPC & PNT2003- for GEP-NETs are the radioligand therapies which will be added to Lily’s portfolio 10 USD 1.3B Merck will expand & diversify its pipeline through this deal CN201, a novel investigational bi-specific antibody will be added to the Merck pipeline CN201 is currently being investigated in Phase 1 and Phase 1b/2 clinical trials for the treatment of patients with relapsed or refractory non-HL and relapsed or refractory B-ALL respectively 11 USD 1B Novartis will strengthen its pipeline for radioligand therapy through this acquisition Novartis will also gain access to RLT research resources that enhance their extensive internal efforts to investigate novel isotopes, combinations MC-339, an actinium-based RLT being investigated in SCLC will also be acquired by Novartis 12 USD 880M Jazz will gain access to worldwide rights for a KRAS inhibitor program Redx has discovered several preclinical KRAS candidates & this deal will help advance candidates through IND-enabling studies MCRPC- Metastatic castration-resistant prostate cancer, GEP-NETs- gastroenteropancreatic neuroendocrine tumors, HL-Hodgkin’s lymphoma, B-ALL- B-cell acute lymphocytic leukemia, SCLC- Small cell lung cell, KRAS-Kirsten rat sarcoma virus Sources- Novartis, Astella, Pharma Tech, Genentech, Lily Page 14

  15. Cancer Compass Advances, Approval & Regulatory Updates ACQUIRER TARGET DEAL SIZE 13 USD 850M Genentech will strengthen the oncology pipeline through this acquisition Preclinical candidate RGT-587, a "Phase 1 ready" will also be included in the deal RGT-587, a CDK4 inhibitor, intended to treat brain metastases 14 USD 680M Deal will broaden Merck’s pipeline of next-generation immunotherapies as its top-seller KEYTRUDA nears the end of US market exclusivity Merck will also gain access to T-cell engagers, including MK-6070 (formerly HPN328) MK-6070 is a T-cell engager targeting delta-like ligand 3, an inhibitory canonical Notch ligand that is expressed at high levels in SCLC and NET. The safety, tolerability, and pharmacokinetics of MK- 6070 are currently being evaluated as monotherapy in a Phase 1/2 clinical trial 15 USD 405M This acquisition will accelerate the availability of COSELA G1’s COSELA is the first and only product approved by the FDA. It is a prescription medicine used to help reduce the occurrence of low blood cell counts caused by damage to bone marrow from chemotherapy COSELA is used to treat adults taking certain chemotherapies (platinum/etoposide or topotecan) for ES-SCLC NET - neuroendocrine tumors, ES- SCLC- Extensive stage Small cell lung cancer Sources- Merck Page 15

  16. Cancer Compass Advances, Approval & Regulatory Updates MERGER Q4 2023- Q3 2024 1 This merger will focus on advancing TuHURA’s innate immune response agonists and tumor microenvironment modulators Planning to initiate a single Phase 3 accelerated approval registration trial in the first half of 2025 with their lead innate immune response agonist, IFx-2 IFx-2 is a personalized cancer vaccine candidate in patients with advanced Merkel Cell Carcinoma or cutaneous Squamous Cell Carcinoma 2 Merger will expand OncoC4’s wholly owned immunotherapy pipeline and establishes in-house clinical manufacturing capabilities AI-071 – A Phase 2 ready, next-generation siglec agonist that is designed for broad siglec coverage with potential application across immunotherapy treated indications Additionally, will gain access to investigational new drug -ready AI-081 & AI-071 AI-081 – A potentially best-in-class bispecific antibody against Programmed Death-1 and vascular endothelial growth factor that has demonstrated high potency and in vivo anti-tumor activity in preclinical models Sources- Kintara Page 16

  17. Cancer Compass Advances, Approval & Regulatory Updates KEY COLLABORATION/PARTNERSHIP Q4 2023- Q3 2024 1) USD 22B Global development and commercialization agreement for three of Daiichi Sankyo’s DXd antibody-drug conjugate candidates: patritumab deruxtecan (HER3-DXd), ifinatamab deruxtecan (I-DXd) and raludotatug deruxtecan (R-DXd) Merck will pay Daiichi Sankyo a $4B upfront payment in addition to $1.5B in continuation payments and may make additional payments of up to $16.5B contingent upon the achievement of future sales milestones 2) USD 8.4B Collaboration will help in co-developing and co-commercializing BL-B01D1 in the US SystImmune will also be eligible to receive up to $7.1B in development, regulatory, and sales performance milestones, on top of tiered royalties on net sales outside the US and Mainland China Bristol Myers Squibb will make an upfront payment of $800M and pledge up to $500M in contingent near- term payments SystImmune will retain exclusive rights in Mainland China and Bristol Myers Squibb will gain an exclusive license in the rest of the world 3) USD 3.5B Collaboration will focus on an innovative approach to combine two powerful technologies to target cancer —antibody-drug conjugation and targeted protein degradation specificity and anti-cancer activity Nurix will receive an upfront payment of $60M and has the potential to receive up to approximately $3.4B in research, development, regulatory, and commercial milestone payments across multiple programs 4) USD 3.1B Collaboration will develop degrader-antibody conjugates, an emerging modality designed to selectively target and neutralize disease-causing proteins in cancer cells C4 Therapeutics will receive $16M upfront and could potentially receive $740M in milestone payments Sources- Merck, BMS, Nurix, C4, Iqvia Page 17

  18. Cancer Compass Advances, Approval & Regulatory Updates 5) USD 2.1B Collaboration will combine Monte Rosa Therapeutics’ highly differentiated QuEENTM discovery engine with Roche’s strong expertise in delivering transformative therapies Monte Rosa Therapeutics will receive an upfront payment of $50M and is eligible to receive future preclinical, clinical, commercial, and sales milestone payments that could exceed $2B, as well as tiered royalties 6) USD 2B Partnership will help in the discovery of novel small-molecule medicines for challenging targets in major disease areas, including oncology and neurodegeneration Orionis will receive an upfront payment of $47M and is eligible for development milestone payments, as well as commercial and net sales milestone payments that could exceed $2B and a tiered royalty upon the sale of collaboration products 7) USD 1.8B Collaboration will combine leading technologies to develop breakthrough, mRNA-enabled in vivo expressed TCER molecules. Companies to leverage Immatics XPRESIDENT target discovery platform and Moderna’s mRNA technology for the development of novel cancer vaccines Moderna will pay $120B upfront payment. Immatics will also be eligible to receive additional cash over $1.7B in a combination of research funding, as well as development, regulatory, and commercial milestone payments & a tiered royalty on global net sales of TCER 8) USD 1.4B Partnership will accelerate the discovery and development of first-in-class antibody-drug conjugate candidates for cancer Merck will pay Caris an undisclosed upfront payment and research funding. As the ADC programs progress, Caris will be in line for up to a total of $1.4B in milestone payments as well as tiered royalties Sources- Roche, Orion, Moderna, Merck Page 18

  19. Cancer Compass Advances, Approval & Regulatory Updates 9) USD 1B Collaboration will support in development of a next-generation antibody-drug conjugatecandidate YL211, targeting c-Mesenchymal epithelial transition factor against solid tumors MediLink will receive an initial $50M in upfront and near-term milestone payments, with the potential for the total deal value to approach $1B, including additional milestone payments and tiered royalties on future global sales 10) USD 547M Collaborate to develop a new type of small-molecule drug for cancer Also, will gain access to NextRNA’s technology to advance two small molecule drugs that target cancers driven by dysregulated long non-coding RNA NextRNA will receive up to $547M for both programs, including upfront and near-term milestone payments, research funding, and development and commercial milestone payments, as well as tiered royalties on future net sales 11) Undisclosed Collaboration will aim to leverage Lantern computational tools to streamline the development process of XCE853 Oregon will utilize the RADR AI platform of Lantern to identify biomarkers and efficacy-linked signatures of XCE853 for precision development across solid As per the deal terms, Lantern will gain equal IP co-ownership and drug development rights for new biomarkers and indications as well as pharmacological usage strategies for XC853 and associated analogs Oregon will receive financial benefits from the out-licensing of the background IP to Lantern Sources- Recursion, Roche, Caris Page 19

  20. Cancer Compass Advances, Approval & Regulatory Updates SOME KEY AI COLLABORATION/ PARTNERSHIP Q4 2023- Q3 2024 1) USD 0.1B Recursion will gain preferred access to one of the largest proprietary, de-identified, patient-focused oncology datasets Goal will be to facilitate the large-scale discovery of potential therapeutics enriched with biomarkers by training causal AI models Recursion will pay Tempus up to $160M in cash or equity for continued and updated data access and use rights for therapeutic development purposes 2) USD 18M AstraZeneca will leverage Immunai’s proprietary technologies, including its immune cell atlas, AMICA, and the Immunodynamics Engine (IDE) to develop cancer drugs Objective will be to enhance clinical decision-making, including dose selection and biomarker identification 3) USD >10M Both companies aim to develop newGemini Digital Twins – innovative tools designed to enhance cancer treatment strategies Objective will be to discover and validate novel drug targets and to develop drug candidates across multiple oncologic indications through the utilization of Aitia's Digital Twins Aitia will be eligible to receive certain upfront payments, and development and regulatory milestone payments totaling more than USD 10M per drug target 4) Undisclosed Collaboration will aim to utilize BioAI's PredictX platform to develop AI-based models specifically focusing on screening biomarkers for colorectal cancer Objective will be to produce a companion diagnostic test for Arbele's drug assets, improving patient selection through advanced AI technology Sources- BioAI, Caris Page 20

  21. Cancer Compass Advances, Approval & Regulatory Updates 5) Undisclosed Takeda to leverage Tempus’ multimodal real-world datasets and biological model systems to advance its cancer therapy pipeline Objective will be to assist in the advancement of Takeda's cancer therapeutics portfolio 6) Undisclosed Moderna will leverage Caris’vast library of de-identified, multi-modal data solutions to support Moderna’s oncology pipeline Collaboration will improve the probability of technical & regulatory success of Moderna’s innovative oncology medicines 7) Undisclosed This collaboration will provide Avacta access to Tempus’ multimodal datasets comprising primary tumor samples and associated clinical data Objective will be to leverage insights to further enhance itsprecision platform with the help of analytical support & computation biology 8) Undisclosed They will identify novel targets with strong disease links, further strengthening Bayer’s precision oncology development portfolio under this collaboration Objective will be to develop AI-powered approaches with applications in precision oncology drug research and development Aignostics will receive an upfront payment and is eligible to receive success-based milestone payments and royalties on any commercialized therapies Sources- Bayer, Takeda Page 21

  22. Cancer Compass Advances, Approval & Regulatory Updates SUMMARY Between September 2023 and September 2024, the FDA and EMA approved 30 notable drugs In the first half of 2024, 6 AI/ML devices were approved, compared to only two in 2023 Approximately 13 of these drugs have been designated as orphan drugs, and 10 are classified as first-in-class Majority of these devices focus on solid tumors, with lung and breast cancers having the highest number of AI devices In the first half of 2024, most approved drugs target lung and blood cancers Most approvals in 2024 primarily consist of companion diagnostic tests Artificial Intelligence (AI) has been extensively explored as a catalyst to accelerate the discovery and design of new drug targets Page 22

  23. Cancer Compass Advances, Approval & Regulatory Updates ONCOLOGY DRUG APPROVALS Q4 2023 - Q4 2024 In the first half of 2024, the FDA approved over 50 new or expanded indications for previously approved agents, along with 18 new oncology agents FDA has approved 9 T cell-engaging bispecific antibodies for the treatment of cancer. Some of these therapeutics have received expanded approvals for the treatment of additional cancers since their first approval in H1 2024 Among these approvals, there are approximately 23 for solid tumors and 9 for hematological malignancies in the first half of 2024 5 treatments have been approved by both the FDA and EMA: Onivyde, Wyost, Alectinib, Imfinzi, and Epkinly, in the first half of 2024 Out of the total FDA approvals in this period, 31 are biologics and 6 are biosimilars Notable Drug Approvals by Types (Q4 2023 – Q3 2024) Notable Drug Approvals by Types (Q4 2023 – Q3 2024) 13 13 12 18 10 Novel Drugs Extended Indication Orphan Expedited First in Class Sources- Aptitude Health , Q2 Page 23

  24. Cancer Compass Advances, Approval & Regulatory Updates Drug approvals (Sep 2023- Sep 2024) Indication: NSCLC Brand Name: LAZCLUZE Lazertinib U Manufactured by Juno Therapeutics Inc, Lisocabtagene maraleucel is a genetically modified autologous T-cell therapy that targets CD19 Used to treat follicular lymphoma and relapsed or refractory MCL. It offers patients with few other treatment options an efficient chimeric antigen receptor T-cell therapy option Indication: Follicular Lymphoma Brand Name: BREYANZI Lisocabtagene Maraleucel U Manufactured by Juno Therapeutics Inc, Lisocabtagene maraleucel is a genetically modified autologous T-cell therapy that targets CD19 Used to treat follicular lymphoma and relapsed or refractory MCL. It offers patients with few other treatment options an efficient chimeric antigen receptor T-cell therapy option Indication: Grade 2 Astrocytoma Brand Name: VORANIGO Vorasidenib U Produced by Servier Pharmaceuticals LLC, Vorasidenib an IDH-1 and IDH-2 inhibitor First genuinely focused treatment for a sizable population of glioma patients, and it is the first approved drug for individuals with low-grade gliomas in almost two decades Indication: Cervical Cancer Brand Name: TIVDAK Tisotumab vedotin-tftv U Manufactured by Seagan Inc, targets a protein called tissue factor that is often highly expressed on the surface of cervical cancer cells On April 29, 2024, the FDA granted traditional approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy Tisotumab vedotin-tftv previously received accelerated approval for this indication in 2021 U US Approval E EMA Approval Orphan Drug First-in-class Expedited EGRF – Epidermal Growth Factor Receptor, NSCLC: Non-small cell lung cancer, IDH: Isocitrate dehydrogenase, MCL: mantle cell lymphoma Sources- FDA, FDA, Pubmed, FDA , FDA, FDA Page 24

  25. Cancer Compass Advances, Approval & Regulatory Updates Indication: MTC with RET Mutation Brand Name: RETEVMO Selpercatinib U Manufactured by Eli Lily, Selpercatinib is a major advancement in targeted therapy for tumors linked to Rearranged during transfection mutations This medication was approved on September 27, 2024. It was earlier authorized for advanced or metastatic thyroid carcinoma with Rearranged during transfection fusion in June 2024 Indication: Multiple Myeloma Brand Name: SARCLISA Isatuximab-irfc U Developed by Sanofi, Isatuximab is an IgG1 monoclonal antibody that binds to the glycoprotein CD38 expressed on the surface of haematopoietic and tumour cells Indicated for the treatment of haematological malignancies. In combination with bortezomib, lenalidomide, and dexamethasone for the treatment of MM Indication: NSCLC with EGFR Brand Name: RYBREVANT Amivantamab-vmjw U Manufactured by Johnson & Johnson, Amivantamab is an anti-EGRF and JNJ-61186372 designed to treat tumors driven by activated EGRF and/or cMet signaling in combination with carboplatin and pemetrexed Indication: Breast Cancer Brand Name: KISQALI Ribociclib U Produced by Novartis, targets proteins called CDK 4 andCDK 6 on breast cancer cells Approved for the adjuvant treatment of stage II and III early breast cancer that is at high risk of recurrence and has a hormone receptor and human EGRF 2 negative Novartis’ win is a direct threat to Eli Lilly’s rival drug Verzenio U US Approval E EMA Approval Orphan Drug First-in-class Expedited MM: Multiple Myeloma, EGRF: Epidermal Growth Receptor Factor, JNJ-61186372: anti-cMet bispecific low fucose antibody with enhanced Fc function, CDK- cyclin dependant kinase Sources- FDA, FDA Page 25

  26. Cancer Compass Advances, Approval & Regulatory Updates Indication: Endometrial Cancer Brand Name: IMFINZI Durvalumab U E Manufactured by Astrazeneca, a cancer immunotherapy that helps the immune system fight cancer cells Durvalumab plus chemotherapy, followed by durvalumab alone, was approved for advanced or recurrent endometrial cancers that have defects in mismatch repair This is durvalumab’s fourth FDA approval and its first for endometrial cancer Indication: Refractory Follicular Lymphoma Brand Name: EPKINLY (US) & TEPKINLY (EU) Epcoritamab U E Manufactured by Genmab, Epcoritamab is a bispecific CD20-directed CD3 T-cell engager & works by binding to a protein called CD3 on healthy T cells and a protein called CD20 on B cells FDA granted accelerated approval to epcoritamab-bysp for relapsed or refractory FL after two or more lines of systemic therapy Indication: Colorectal Cancer Brand Name: KRAZATI Adagrasib U Developed by Mirati Therapeutics Inc, Adagrasib is an inhibitor of G12C mutated KRAS Adagrasib was granted accelerated approval for use in combination with cetuximab for KRAS G12C-mutated locally advanced or metastatic colorectal cancer. This marked the first approval for a KRAS inhibitor specifically targeting KRAS G12C mutations in colorectal cancer In the first quarter of 2024, it had $21M in sales Indication: Melanoma Brand Name: AMTAGVI Lifileucel U Developed by Lovance Therapeutics Inc, Lifileucel is a tumor-derived autologous T cell immunotherapy, Granted accelerated approval as a second-line treatment for PD-1 blocking antibody and, if BRAF V600 positive, a BRAF inhibitor with or without a Methyl ethyl ketone inhibitor FDA also decided to make lifileucel the first cellular therapy to be approved for a solid tumor, the skin cancer melanoma Q2 2024 represents the first quarter of Amtagvi sales in the US with product revenue of $12.8M, which is only recognized upon patient infusion CD- cluster of differentiation, FL: follicular lymphoma, KRAS: Kirsten rat sarcoma viral oncogene homolog GTPase, BRAF: B-Raf proto-oncogene, serine/threonine kinase U US Approval E EMA Approval Orphan Drug First-in-class Expedited Sources- Aptitude Health, FDA, FDA, FDA, FDA Page 26

  27. Cancer Compass Advances, Approval & Regulatory Updates Indication: Bladder Cancer Brand Name: ANKTIVA Nogapendekin alfa inbakicept-pmln U Manufactured by Altor Biosciences LLC, Nogapendekin alfa inbakicept-pmln activates the IL- 15 receptor on the surface of some immune cells, including T cells and natural killer cells. This was the first approval and it’s the first IL-15 receptor agonist to be approved by the FDA Indication: ALK-Positive NSCLC Brand Name: ALECENSA Alectinib U Manufactured by Genentech, Alectinib blocks the activity of anaplastic lymphoma kinase Approved for adjuvant treatment following tumor resection in patients with AL kinase- positive NSCLC tyrosine kinase Kinase inhibitor generated $1.6B in revenue in 2023 Indication: Metastatic NSCLC Brand Name: TEPMETKO Tepotinib U Manufactured by EMD Serono, Inc, it is an anti-cancer medication used for the treatment of adults with NSCLC Indicated for metastatic NSCLC whose tumors have an abnormal MET gene Tepotinib was previously granted accelerated approval on February 3, 2021, but it was converted to traditional approval Indication: ES-SCLC Brand Name: IMDELLTRA Tarlatamab-dlle U Manufactured by Amgen, It works by binding to a protein called CD3 on healthy T cells and a protein called Delta-like ligand 3 on SCLC FDA granted accelerated approval for extensive-stage SCLC with disease progression on or after platinum-based chemotherapy & is a first-in-class, bispecific delta-like ligand 3 directed CD3 T cell engager U US Approval E EMA Approval Orphan Drug First-in-class Expedited AL: anaplastic lymphoma, NSCLC: Non-small cell lung cancer, MET:mesenchymal-epithelial transition, SCLC: Small cell lung cancer Sources- FDA , PRN Page 27

  28. Cancer Compass Advances, Approval & Regulatory Updates Indication: ESCC Brand Name: TEVIMBRA Tislelizumab-jsgr U E Manufactured by BiGene Ltd, Tevimbra is a humanized IgG4 anti-PD-L1 antibody designed to aid the body’s immune cells in detecting and fighting tumors Approved for unresectable or metastatic esophageal squamous cell carcinoma following prior systemic chemotherapy Also approved by Israel in Sep 2024 Indication: Breast Cancer Brand Name: TRUQAP Capivasertib U E Developed by AstraZeneca, Capivasertib is a serine/threonine kinase inhibitor Approved in combination with fulvestrant hormone receptor-positive, human epidermal growth factor receptor 2–negative locally advanced or metastatic breast cancer It was the first protein kinase B inhibitor to cross the FDA finish line Indication: Urothelial Cancer Brand Name: BALVERSA Erdafitinib U E Developed by Johnson & Johnson, Erdafitinib is a fibroblast growth factor receptor tyrosine kinase inhibitor Approved for locally advanced or metastatic urothelial carcinoma with susceptible Fibroblast growth factor 3 genetic alterations Erdafitinib was the first targeted therapy to receive a positive CHMP recommendation in Europe Indication: NSCLC Brand Name: CEJEMLY Sugemalimab E Manufactured by Cstone Pharmaceutical , Sugemalimab block the interaction between PD-1 and PD-L1, and to induce antibody-dependent cellular phagocytosis EMA approved the world's first anti-PD-L1 monoclonal antibody for first-line treatment of both squamous and non-squamous NSCLC, also marking the first successful international approval of a China domestic anti-PD-L1 mAb U US Approval E EMA Approval Orphan Drug First-in-class Expedited NSCLC: Non-small cell lung cancer, PD-L1: Programmed Death Ligand-1 Sources- Amgen, ecancer, Cstone Page 28

  29. Cancer Compass Advances, Approval & Regulatory Updates Indication: FL & B-cell Lymphoma Brand Name: ORDSPONO Odronextamab E Produced by Regeneron Pharmaceutical, Odronextamab is a human monoclonal antibody that triggers T-cell-mediated cytotoxicity EMA granted conditional marketing authorization for the medicinal product Ordspono, a bispecific antibody that acts by linking the lymphoma cell to a killer T cell Indication: Solid Tumors Brand Name: AUGTYRO Repotrectinib U E Manufactured by Bristol Myers Squibb, Repotrectinib is a novel ROS1/TRK tyrosine kinase inhibitor FDA granted accelerated approval to repotrectinib (brand name Augtyro) for the treatment of solid tumors- NTRK fusion-positive solid tumors & ROS1-positive NSCLC BMS got Augtyro through its $4.1B acquisition of Turning Point Therapeutics in 2023 Indication: Metastatic Colorectal Cancer Brand Name: FRUZAQLA Fruquintinib U E Manufactured by Takeda, Fruquintinib is an oral inhibitor of vascular EGRF1/2/3 Approved for metastatic colorectal cancer who received prior FOLFOXIRI US in-market sales of $130.5M in the first half of 2024 – demonstrating strong demand and commercial traction since launch Received Japanese approval in 2024 Indication: Nasopharyngeal Carcinoma Brand Name: LOQTORZI Toripalimab-tpzi U E Produced by Coherus Biosciences, Toripalimab is a humanized IgG4 monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2 First and only FDA-approved as a single agent for recurrent unresectable or metastatic Nasopharyngeal carcinoma with disease progression on or after a platinum-containing chemotherapy Net sales in Q2 2024 of $3.8M U US Approval E EMA Approval Orphan Drug First-in-class Expedited NSCLC: Non-small cell lung cancer, PD-L1: Programmed Death Ligand-1, EGRF- Epidermal Growth Receptor factor, NTRK-neurotrophic tyrosine receptor kinase, FOLFOXIRI: combination of fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy Sources- EMA, FDA, Pubmed, Esmo Page 29

  30. Cancer Compass Advances, Approval & Regulatory Updates Indication: Lymphoblastic Leukemia Brand Name: BLINCYTO Blinatumomab U Produced by Amgen, Blincyto targets malignant and benign B cells via the CD19 cell surface antigen while simultaneously engaging the patient’s T cells through the CD3 antigen Approved for CD19-positive Philadelphia chromosome-negative B-cell precursor ALL Indication: Myelodysplastic Syndromes Brand Name: RYTELO Imetelstat U Manufactured by Geron Corporation, Imetestat first-in-class treatment that works by inhibiting telomerase enzymatic activity FDA approved imetelstat for low- to intermediate-1 risk myelodysplastic syndromes with transfusion-dependent anemia Rytelo is expected to generate $54M in revenue in 2024 Indication: Brain Cancer Brand Name: OJEMDA Tovorafenib U Manufactured by Day One Pharmaceutical, Tovorafenib functions as a Type II RAF kinase inhibitor, targeting mutant BRAF V600E, wild-type BRAF, and wild-type CRAF kinases FDA granted accelerated approval for relapsed or refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement, or BRAF V600 mutation Achieved $8.2M net product revenue in initial 2 months of launch Indication: GEP-NETs Brand Name: LUTATHERA Lutetium Lu 177 dotatate U Produced by Novartis, works by binding to somatostatin receptors on tumor cells, entering the cells, and releasing a radioactive particle that kills them Approved for GEP-NETs that express the somatostatin receptor (SSTR) U US Approval E EMA Approval Orphan Drug First-in-class Expedited ALL: acute lymphoblastic leukemia Sources- EMA, FDA, Pubmed, Esmo Page 30

  31. Cancer Compass Advances, Approval & Regulatory Updates Indication: Malignant Pleural Mesothelioma Brand Name: KEYTRUDA Pembrolizumab U Produced by Merck, works by binding PD-1 on T cells, thereby preventing PD-L1 on cancer and other cells from engaging with PD-1 and inactivating T cells Approved in combination with pemetrexed and platinum chemotherapy as first-line treatment of unresectable advanced or metastatic malignant pleural mesothelioma On February 22, 2024, EMA recommended extending the marketing authorization for pembrolizumab to include the treatment of resectable NSCLC Indication: Pancreatic Adenocarcinoma Brand Name: ONIVYDE Irinotecan liposome U E Manufactured by Ipsen Biopharmaceutical, Onivyde is a antitumor activity by forming a complex with topoisomerase I and blocking its enzymatic activity, thereby interfering with DNA synthesis Approved in combination with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma Onivyde generated $1.77B sales in H1 2024 U US Approval E EMA Approval Orphan Drug First-in-class Expedited NSCLC: Non –small cell Lung cancer, GEP-NET: gastroenteropancreatic neuroendocrine tumors Sources- EMA, FDA, Page 31

  32. Cancer Compass Advances, Approval & Regulatory Updates BIOSIMILAR APPROVED IN Q4 2023- Q3 2024 AVZIZI U E Reference Drug - AVASTIN Approved as fifth bevacizumab biosimilar, Avzivi is a humanized mAb that inhibits vascular endothelial growth factor Approved for indications- colorectal cancer, NSCLC, glioblastoma, RCC, cervical cancer & Ovarian cancer WYOST & JUBBONTI U E Reference Drug - XGEVA & PROLIA First, Biosimilar approved preventing RANKL from activating its receptor, RANK on the surface of osteoclasts, their precursors, and osteoclast-like giant cells Wyost for multiple myeloma and bone metastases from solid tumors & Jubbonti for postmenopausal women with osteoporosis U US Approval E EMA Approval RANK: receptor activator of nuclear factor-Κb, NSCLC: Non-small cell lung cancer, RCC: Renal Cell Cancer, EGRF: Epidermal Growth Receptor Factor, EMT: epithelial–mesenchymal transition, MET: mesenchymal–epithelial transition Sources- FDA, FDA, FDA Page 32

  33. Cancer Compass Advances, Approval & Regulatory Updates GENERICS APPROVED IN Q4 2023- Q3 2024 PALBOCICLIB U E Brand Name - IBRANCE Palbociclib is a cancer growth blocker that works by blocking the proteins CD 4 and 6 on cancer cells Approved for hormone receptor-positive, human EGRF- 2 negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy or Fulvestrant ERIBULIN MESYLATE U E Brand Name - HALAVEN Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from EMT to MET states Approved for metastatic breast cancer who have previously received at least two chemotherapeutic regimens; unresectable or metastatic liposarcoma U US Approval E EMA Approval RANK: receptor activator of nuclear factor-Κb, NSCLC: Non-small cell lung cancer, RCC: Renal Cell Cancer, EGRF: Epidermal Growth Receptor Factor, EMT: epithelial–mesenchymal transition, MET: mesenchymal–epithelial transition Sources- FDA, FDA, FDA Page 33

  34. Cancer Compass Advances, Approval & Regulatory Updates ONCOLOGY TOOLS / DEVICES APPROVALS Q4 2023- Q3 2024 FDA approved AI/ML –enabled device 250 221 200 158 130 150 113 107 80 100 64 26 50 18 6 0 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 (H1) FDA has authorized 107 devices so far in H1 2024, which is on track to meet 2023’s mark About 97% of AI-enabled devices on the list were 510(k) cleared as of August 2024 Tools/devices endorsed for oncology, specifically target lung cancer followed by breast, prostate cancer & Tumors Dermasensoris the first AI enabled device that helps to detect all 3 common skin cancers- Melanoma, Basal Cell cancer & Squamous cell cancer Hologics Genius Digital Diagnostics System is the first digital cytology system for cervical cancer screening FDA approved AI/ML –enabled device A total of 11 devices have been granted approval by FDA till Sep 2024 out of which 6 are AI-enabled 2023 2024 6 EasySep Human Bone Marrow CD138+ Selection Kit received de novo classification as a Class II in vitro diagnostic device for hematopoietic cell enrichment 5 4 3 BRAHMS CgA II Kryptor, the first and only FDA- cleared Chromogranin A test and the only automated immunoassay worldwide for the assessment of tumor progression in GEP-NET 2 1 2 6 4 5 0 AI/ML enabled CE certified (September) GEP-NET: gastroenteropancreatic neuroendocrine tumor Sources- MedtechDive Page 34

  35. Cancer Compass Advances, Approval & Regulatory Updates ONCOLOGY TOOLS / DEVICES APPROVALS Q4 2023- Q3 2024 F A Indication : AI solution for Lung cancer QCT LN Quant Approved as a AI system to analyze lung nodules on non-contrast chest CT scans and track volumetric growth as part of monitoring progress With end-to-end AI solutions for lung health identification, measurement, management, and monitoring, qCT LN Quant becomes a part of the Qure.ai US AI-powered Lung Cancer care continuum F E Indication : In-vitro diagnostic test for NSCLC patients TruSight Oncology (TSO) Comprehensive Assay First FDA-approved diagnostic tool for locally advanced or metastatic rearranged during transfection fusion-positive non-small cell lung cancer who might benefit from selpercatinib (RETEVMO) treatment, as well as those with NTRK-positive solid tumors who might benefit from larotrectinib (VITRAKVI) F A E Indication : Hand-held device for skin cancer detection DermaSensor First AI-Powered Medical Device to Detect All Three Common Skin Cancers (Melanoma, Basal Cell Carcinoma and Squamous Cell Carcinoma) DermaSensor uses elastic scattering spectroscopy to evaluate the cellular and subcellular characteristics of suspicious skin lesions F A E Indication : AI enabled Diagnostic for cervical cancer cells Genius Digital Diagnostics System First digital cytology system approved for Cervical cancer screening Use deep-learning-based artificial intelligence and advanced volumetric imaging technology E : CE certified tools A : AI\ML enabled devices oncology specific F : FDA approved Sources- MedtechDive, Qure ai, Iiumina, DermaSensor, Hologics Page 35

  36. Cancer Compass Advances, Approval & Regulatory Updates F A E Indication : CDx Liquid Biopsy for NSCLC & Breast Cancer Guardant360 Approved for Tumor mutation profiling with any solid cancerous tumor and for companion diagnostic indications to identify who might benefit from certain targeted therapies for advanced non-small cell lung cancer and breast cancer F Indication : Companion Diagnostics for Prostate Cancer FoundationOne CDx & FoundationOne Liquid CDx Approved as companion diagnostics for olaparib (LYNPARZA) plus abiraterone acetate (ZYTIGA) and prednisone or prednisolone for deleterious or suspected deleterious breast cancer gene-mutated mCRC F Indication : Companion Diagnostic for Synovial sarcoma MAGE-A4 IHC 1F9 pharmDx Approved as companion diagnostic for various cancers, including synovial sarcoma Its an immunohistochemistry assay used to detect MAGE-A4 expression in formalin-fixed, paraffin-embedded synovial sarcoma tissue. MAGE-A4 positivity in synovial sarcoma is a biomarker of eligibility for treatment with TECELRA F Indication : Companion Diagnostic for Synovial Sarcoma SeCore CDx HLA A Sequencing System Approved as a companion diagnostic for afamitresgene autoleucel (afami-cel; TECELRA) for previously treated advanced synovial sarcoma E : CE certified tools A : AI\ML enabled devices oncology specific F : FDA approved MCRC: metastatic castration-resistant prostate cancer Sources- Guardant, FoundationOne, Agilent, One Lamba, FDA Page 36

  37. Cancer Compass Advances, Approval & Regulatory Updates F A Indication : Prostate cancer diagnosis AI solution Medihub Prostate Got approved for prostate cancer Its an artificial intelligence-based medical solution that detects suspected prostate cancer areas through analysis of Multi-Sequence prostate MRI and assists in diagnosing prostate cancer F A E Indication : Detection system using AI for Colon cancer GI Genius intelligent endoscopy Approved to detect colorectal polyps through enhanced visualization during colonoscopy. Its first-to-market, computer-aided polyp detection system powered by AI By harnessing deep learning algorithms and real-time data, GI Genius detects and estimate possible histology of colorectal polyps through enhanced visualization in White Light colonoscopy F Indication : IVD for Multiple Myeloma EasySep Human Bone Marrow CD138+ Selection Kit Kit received de novo classification as a Class II in vitro diagnostic device for hematopoietic cell enrichment, aimed at enhancing the sensitivity of diagnostic tests for conditions like multiple myeloma This classification marks it as a first-of-its-kind product in this category F Indication : Non invasive platform for Liver tumor HistoSonics Edison System Received De Novo clearance and designated as breakthrough device , marking it as a significant advancement in non-invasive tumor treatment This approval enables its use for partial or complete destruction of unresectable liver tumors E : CE certified tools A : AI\ML enabled devices oncology specific F : FDA approved Sources- JLK, Medtronic Page 37

  38. Cancer Compass Advances, Approval & Regulatory Updates F Indication : Companion Diagnostic to identify AML Abbott RealTime IDH1 Indicated as an aid in identifying acute myeloid leukemia and myelodysplastic syndrome with an isocitrate dehydrogenase-1 mutation for treatment with ivosidenib (TIBSOVO) or in identifying AML patients for treatment with olutasidenib (REZLIDHIA) F Indication : Companion Diagnostic for Breast Cancer FoundationOne CDx Approved as a companion diagnostic for AstraZeneca’s TRUQAP (capivasertib) in combination with FASLODEX (fulvestrant) approved for hormone receptor-positive, human EGRF 2 negative locally advanced or metastatic breast cancer F Indication : Companion Diagnostic for Solid Tumor FoundationOne CDx Approved as a companion diagnostic for Eli Lilly and Company’s RETEVMO (selpercatinib), for locally advanced or metastatic solid tumors with a RET gene fusion F Indication : Companion Diagnostic for NSCLC FoundationOne CDx Approved as companion diagnostics for Pfizer’s encorafenib (BRAFTOVI) in combination with binimetinib (MEKTOVI) for metastatic NSCLC with a serine/threonine-protein kinase B-Raf V600E mutation E : CE certified tools A : AI\ML enabled devices oncology specific F : FDA approved NSCLC: Non- small cell lung cancer, EGRF: Epidermal Growth Receptor Factor, AML:acute myeloid leukemia Sources- Foundation Medicine, Solid Tumor, NSCLC Page 38

  39. Cancer Compass Advances, Approval & Regulatory Updates F E Indication : Diagnostic tool for GEJ PD-L1 IHC 22C3 pharmDx Approved as diagnostic tool to aid in identifying patients with Gastric or Gastroesophageal Junction Adenocarcinoma who might be eligible for treatment with KEYTRUDA F Indication : IVD test to analyze cancerous genes Invitae Common Hereditary Cancers Panel Received as de novo marketing authorization Test analyzes 47 genes, including BCR1 and BCR 2, which are associated with an increased risk of breast and ovarian cancer Also includes genes linked to Lynch syndrome, an inherited condition that increases the risk of various cancers F E Indication : Biomarker test for Non invasive bladder cancer Bladder EpiCheck Approved as a noninvasive method for surveillance of tumor recurrence in previously diagnosed non–muscle invasive bladder cancer ,in conjunction with cystoscopy First methylation-based urine test performed on a quantitative polymerase chain reaction platform & also commercially available in Europe F E Indication : Automated immunoassay for GEP-NET BRAHMS CgA II Kryptor First and only FDA-cleared Chromogranin A test and the only automated immunoassay worldwide for the assessment of tumor progression in GEP-NET E : CE certified tools A : AI\ML enabled devices oncology specific F : FDA approved GEP-NET: Gastroenteropancreatic neuroendocrine tumor, BCR: Breast cancer gene Sources- JLK, Medtronic Page 39

  40. Cancer Compass Advances, Approval & Regulatory Updates SUMMARY Approximately 622 clinical trials have started in solid tumors, and 18 in hematological cancer Highest number of FDA-approved breakthrough designations has been given for breast cancer, bladder cancer, and blood cancers (lymphoma and leukemia) Gastrointestinal (GI) cancers have moved from sixth to second place among the top indications, indicating their growing significance European Medicines Agency (EMA) has granted the most PRIME designations for lymphoma and rare blood cell cancer indications. Phase 2 trials represent the largest segment of oncology trials at 50.7%, with a notable focus on lung cancer There are around 127 drugs currently in phase 4 trials, making it the smallest segment of oncology trials Page 40

  41. Cancer Compass Advances, Approval & Regulatory Updates ONCOLOGY CLINICAL TRIALS Q4 2023 – Q3 2024 Q4 2023 – Q3 2024 Phase 2 trial, makes up the largest portion of oncology trial phases Approximately 622 & 18 clinical trial started in Solid Tumors & Hematological cancer respectively Phase 1 1447 Approximately 150 ADCs are undergoing various-stage trials, 12% are in the late- stage phase, showcasing rapid advancements Early Phase1 157 Phase 4 127 Phase 2 2376 Phase 3 578 Data as of Sep 2024 Top 10 oncology indication in clinical trial 400 3 65 4 300 6 33 8 2 53 137 40 31 200 2 140 13 9 6 118 104 95 20 7 18 76 67 61 56 100 55 159 105 96 95 99 66 74 75 73 53 0 Lung GI Skin Breast Lymphoma Head & Neck Leukemia Colorectal Ovarian Prostate Phase 1 Phase 2 Phase 3 Phase 4 Data from Sep 2023 - Sep 2024 Clinical trials are increasingly focusing on lung cancer (364 trials), followed by gastrointestinal (GI) cancer Gastrointestinal indications were ranked sixth in clinical trials according to our Healthark Oncology Report 2023. However, in 2024, they have moved up to second place, indicating their growing importance Pfizer leads in the number of breast cancer drugs currently under development. Most of these drugs are in Phase 3 trials for stage 4 metastatic breast cancer, with a strong emphasis on HER2- directed therapies as of October 2024 Merck has the largest number of drugs in development for lung cancer, with most of them in Phase 3 and Phase 2 trials. These trials primarily target stage 2 and 3 resectablelung cancer, as well as stage 4 unresectable lung cancer Sources- Clinical Trial, Iqvia Page 41

  42. Cancer Compass Advances, Approval & Regulatory Updates BREAKTHROUGH THERAPY & PRIME DESIGNATIONS FDA approved Breakthrough therapy designations 2024 01 GDC-0077 Approved in combination with palbociclib (IBRANCE) and fulvestrant (FASLODEX) for the treatment of patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer harboring a PI3Kα mutation following recurrence on or within 12 months of completing adjuvant endocrine therapy 02 NVL-655 Sunvozertinib Novel brain-penetrant ALK-selective tyrosine kinase inhibitors NVL-655 for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who have previously received 2 or more ALK tyrosine kinase inhibitors 03 MCLA- 198 Petosemtamab Approved for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma who have experienced disease progression following treatment with platinum-based chemotherapy and a PD-L1 /PD-1 inhibitor 04 Asciminib Approved for the treatment of adult patients with newly diagnosed in Ph+ CML chronic phase Nogapendekin alfa inbakicep 05 Approved in combination with BCG for adult patients with BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors BCG:Bacillus Calmette-Guérin, Ph+ CML: Philadelphia chromosome-positive chronic myeloid leukemia, NSCLC: Non- small cell lung cancer, ALK:anaplastic lymphoma Kinase, PI3Kα : phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha mutation Sources- FDA, FDA, Cancer Research Page 42

  43. Cancer Compass Advances, Approval & Regulatory Updates 06 T-DXd Approved for treatment of patients with unresectable HR+/HER2-low or -ultralow breast cancer who have received either 2 lines of endocrine therapy in the metastatic setting or 1 line of endocrine therapy 07 KO-539 Ziftomenib Approved for treatment of heavily pretreated patients with relapsed/refractory NPM1-AML marking this agent as the first investigational treatment to be granted breakthrough therapy designation for NPM1- mutated AML 212Pb- Dotamtate 08 AlphaMedix Approved for the treatment of patients with unresectable or metastatic, progressive somatostatin receptor-expressing GEP-NET who have not previously received peptide receptor radioligand therapy Cretostimogene Grenadenorepvc 09 CG0070 Potential therapeutic option in patients with high-risk BCG -unresponsive non-muscle invasive bladder cancer with carcinoma in situ with or without Ta or T1 tumors BCG:Bacillus Calmette-Guérin, FL: follicular lymphoma, GEP-NET: gastroenteropancreatic neuroendocrine tumors, NPM1-mutated AML: nucleophosmin 1-mutant acute myeloid leukemia Sources- Cancer Research, WU-CART, CLR 131 Page 43

  44. Cancer Compass Advances, Approval & Regulatory Updates FDA approved Breakthrough therapy designations Q4 2023 Epcoritamab- bysp 10 Approved for treatment for patients with relapsed/refractory FL previously treated with at least 2 lines of therapy 11 TAR-200 NA Potential future treatment of patients with BCG -unresponsive high-risk non-muscle-invasive bladder cancer, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder) EMA approved PRIME designations 2024 12 WU-CART-007 NA Approved for treatment of patients with relapsed/refractory T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma EMA approved PRIME designations Q4 2023 13 Iopofosine I-13 CLR 131 Approved for Waldenström macroglobulinemia in patients who previously received at least 2 treatment regimens BCG:Bacillus Calmette-Guérin, FL: follicular lymphoma Sources- Cancer Research, WU-CART, CLR 131 Page 44

  45. Cancer Compass Advances, Approval & Regulatory Updates SUMMARY Antibody-drug conjugates (ADCs), radioligand therapies (RLTs), and bi- or multi-specific therapies have experienced significant growth, with a compound annual growth rate (CAGR) that surpasses the overall oncology market Development of ADCs has accelerated notably in recent years, with HER2 and TROP2 being the primary targets, accounting for up to 23% of the focus There are currently nearly 100 ongoing clinical trials targeting prostate and neuroendocrine tumors, where ligand affinity is most effective to date Generative AI techniques have demonstrated remarkable capabilities in medical imaging, producing synthetic medical images, enhancing image quality, and even predicting tumor progression Page 45

  46. Cancer Compass Advances, Approval & Regulatory Updates CLINICAL AND COMMERCIAL SUCCESS MAKES HIGHLY ATTRACTIVE INVESTMENT IN ADCS Pharmaceutical interest in antibody-drug conjugates (ADCs) has surged in recent years, resulting in a wave of new market entrants. Innovations in next-generation ADCs, which employ advanced linker and conjugation technologies, have fueled this renewed enthusiasm. Blockbuster drugs like Gilead's Trodelvy and Daiichi Sankyo and AstraZeneca's Enhertuexemplify the significant commercial potential of ADCs, generating billion-dollar sales in oncology. As a result, ADCs have become a key technology in life sciences, prompting several high-profile deals FDA accepted the BLA of AstraZeneca & Daiichi Sankyo's Datopotamab Deruxtecan (Dato-DXd), granted priority review to Daiichi Sankyo and Merck's patritumab deruxtecan (HER3-DXd) in 2024, whereas AbbVie's Telisotuzumab vedotin (ABBV-399) is expected to get its first approval by 2025 Total Value of ADC Deals (USDB) 200 167 150 107 100 47 50 0 2022 2023 2024 (H1) Licensors from China and Korea make up nearly 60% of partnering deals positioning themselves as significant contributors to ADC research and development in an effort to solidify their roles in this lucrative market. Conversely, companies that in-licensed ADCs are primarily based in the US and Europe, accounting for over 55% of the partnership deals that year More than 90% of ADC partnership deals target oncology indications, mainly for treating breast, lung, and ovarian cancers. Additionally, around 70% of these deals involve ADCs or ADC technologies in the discovery or preclinical development stages in 2024 Pfizer's $43B acquisition of Seagen and AbbVie's $10.1B buyout of ImmunoGen are two of the most notable acquisitions involving antibody–drug conjugate Sources- FDA, Clarivate, Biopharma, NJ, Novotech, Iqvia Page 46

  47. Cancer Compass Advances, Approval & Regulatory Updates ADC Pipeline presence by companies 8 8 7 7 5 5 5 4 4 3 3 2 1 1 AbbVie & Jiangshu Hengrui have the highest ADCs in their drug pipeline (8) followed by others like AstraZeneca (7), Daiichi Sankyo (7), Pfizer (5), GSK (4) ADC Pipeline presence by companies Human EGRF 2 is the primary target in the clinical- stage ADC pipeline, followed by TROP2 and B7- H3.TROP2-directed ADCs show promise in recurrent gynecological cancers HER2 TROP 2 15% 8% 6% B7-H3 FR alpha Others 66% 4% n=140 (Phase 1 to 3) Data as of July 2024 Global Sales (USD B) ADCs maintain their value post-patent expiration and, as biologics, are less affected by the US Inflation Reduction Act, making them attractive amid current industry challenges which will result in increasing sales worldwide 40% 14.9 10.6 7.8 2022 2023 2024F NSCLC: Non-small cell lung cancer, EGRF: Epidermal Growth Receptor Factor, TROR 2:Trophoblast surface antigen 2-directed Sources- FDA, Iqvia, Clarivate, Biopharma, NJ, Novotech Page 47

  48. Cancer Compass Advances, Approval & Regulatory Updates RADIOLIGAND THERAPIES: NOVEL MODALITY AT THE FOREFRONT OF ONCOLOGY INNOVATION Recent deals highlight the increasing interest in the radioligand therapy (RLT) modality, particularly for alpha-emitting candidates. AstraZeneca, Bristol Myers Squibb, and Eli Lilly have all made significant investments to acquire clinical-stage RLT companies, with the highest prices paid for alpha RLT firms like RayzeBio and Fusion Pharmaceuticals. Radioligands can be used for both imaging and treatment RLT in development by isotope Beta-emitting Lu-177 is the primary isotope for radioligand therapies currently in development, accounting for 32% of RLT pipeline assets Other 28% 32% Lu-177 Clinical trials like NCT04104928 are assessing the use of 177Lu-DOTATATE in NSCLC n=121 (Phase 1 to 3) Concurrently, other studies are examining RLTs effectiveness for human EGRF 2-positive breast cancer and colon cancer. These research efforts will open the door for radioligand therapy to be applied to a wide range of solid tumors, greatly increasing its market potential and solidifying its role as a flexible treatment option in oncology 6% I-131 13% 21% Bi-212 Ac-225 Data as of July 2024 RLT in development by isotope Global Sales (USD B) 2.3 Other 22% 39% 41% Prostate n=164 1.6 (Phase 1 to 3) Pancreas 5% 7% NSCLC 0.7 7% Breast 18% NEC 2022 2023 2024F Data as of July 2024 NEC – Neuroendocrine Around 24 studies in 2024 are actively ongoing as compared to 4 studies last year & most of them are for prostate cancer Novartis has the highest RLT in its pipeline (7) followed by Telix & ITM (5) NSCLC: Non- small cell lung cancer, HL: Hodgkin’s lymphoma, MM: multiple myeloma, EGRF: Epidermal Growth Receptor Factor Sources- Iqvia Page 48

  49. Cancer Compass Advances, Approval & Regulatory Updates FUTURE DIRECTION FOR RLTS New ligands with improved specificity and affinity for the target site can reduce toxicity. They can also incorporate stimulus-responsive release systems, such as pH- or redox-sensitive nanoparticle carriers that react to the particular tumor microenvironment 1 New targets: Investigating new receptors to guide RLTs and broaden their use in new tumors, such as gastrin-releasing peptide receptors, chemokine receptor type 4, neurokinin receptor 1, which has been shown to be overexpressed in primary malignant gliomas 2 Combination therapy, which use the synergy of several MoAs, such as upregulating target receptors to boost RLT cellular absorption; increasing the effectiveness of RLTs by blocking DNA repair, such as with PARP or topoisomerase inhibitors; and radio sensitization by blocking other crucial processes 3 Theranostics: Combining therapeutic drugs with radionuclide-based diagnostic imaging to precisely identify patients who will benefit the most, find tumors, customize RLT therapy, and track response 4 NEC – Neuroendocrine Sources- Kintara Page 49

  50. Cancer Compass Advances, Approval & Regulatory Updates BI/MULTI-SPECIFIC ANTIBODIES: POTENTIAL TO SERVE AS A VERSATILE TOOL IN CANCER IMMUNOTHERAPY Bispecific antibodies represent a novel and potentially effective approach in cancer immunotherapy. T- cell engagement which is the primary mechanism of action in cancer immunotherapy, lead the mechanism of action in the clinical-stage pipeline for bi- and multi- specific therapies, accounting for 34% of the total followed by dual checkpoint inhibitor (19%) Bispecific antibody in development by Tumor type Undisclosed 7% Solid tumors, which make 69% of bispecific antibodies in development & mostly investigated targets are PD1/PD-L1, CTLA-4, & EGRF whereas 24% target BCMA, CD-19 & CD-20 Haematological cancer 24% n=283 (Phase 1 to 3) Around 52 studies are going on in H1 2024 out of which 23 are across a range of cancers, with MM and non-HL having significant development in hematological cancers and NSCLC and colorectal cancer in solid tumors 69% Solid Tumor Data as of July 2024 Global Sales (USD B) Regeneron has the highest bi-specific antibodies in its pipeline (12) followed by others like Roche (11), Johnson & Johnson (8), Genmab (6) 2.5 Increasing collaboration in bispecific antibody among major pharmaceutical companies, such as BioNTech with Biotheus, Astellas with Elpiscience, Gilead with Merus, and Johnson & Johnson with Numab, reflects the heightened interest within the pharmaceutical industry 48% 1.6 0.8 2022 2023 2024F NSCLC: Non- small cell lung cancer, HL: Hodgkin’s lymphoma, MM: multiple myeloma, EGRF: Epidermal Growth Receptor Factor, CTLA-4: Cytotoxic T-lymphocyte antigen 4, BCMA:B-cell maturation antigen Sources- Iqvia Page 50

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