Claire Neilan

<!-- Content start --> South San Francisco, CA — July 3, 2024 — Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the Phase II/III SKYSCRAPER-06 study, evaluating tiragolumab plus Tecentriq® (atezolizumab) and chemotherapy versus pembrolizumab and chemotherapy as an initial (first-line) treatment for people with previously untreated, locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (nSq NSCLC), did not meet its primary endpoints of progression-free survival (PFS) at its primary analysis with a hazard ratio (HR) of 1.27 [95% CI: 1.02,1.57] and overall survival (OS) at its first interim analysis with a HR of 1.33 [95% CI: 1.02, 1.73], which was immature. The combination of tiragolumab plus Tecentriq and chemotherapy showed reduced efficacy in both PFS and OS compared to the comparator arm in the intent-to-treat population, which includes Phase II and Phase III cohorts. The overall safety profile remains consistent with the safety profile previously observed for the combination of tiragolumab plus Tecentriq and chemotherapy, and no new or unexpected findings were identified. Based on these results, patients and investigators will be unblinded and we intend to halt the study. A communication will be sent to the investigators and results will be shared with health authorities and subsequently presented at an upcoming medical meeting. “These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic non-squamous lung cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We are thankful to all of the patients and healthcare professionals involved in the study, and we will leverage the learnings to inform our scientific understanding of the anti-TIGIT pathway and new avenues in cancer research.” Ongoing Phase III studies are investigating treatment settings and indications distinct from SKYSCRAPER-06. Based on today’s results, we will evaluate any relevant changes needed to the ongoing tiragolumab program. About SKYSCRAPER-06 study SKYSCRAPER-06 is a global Phase II/III, randomized, placebo-controlled and double-blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) and chemotherapy as an initial (first-line) treatment versus pembrolizumab and chemotherapy in 542 people with non-squamous non-small cell lung cancer. Primary endpoints are overall survival (OS) and progression-free survival (PFS). About tiragolumab Tiragolumab is an investigational novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer. Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq® (atezolizumab). The TIGIT pathway is distinct but

1

David Epstein, the former CEO of Seagen, is at the helm of Ottimo Pharma, a company focused on advancing a PD1-VEGFR2 bi-functional antibody targeting cancer treatment. Backed by Medicxi and led by a seasoned team, Ottimo has secured a significant $140M in #SeriesA funding to propel its lead program, #Jankistomig, into clinical development. This milestone highlights the growing interest in innovative oncology therapies, particularly in the antibody space. With operations in both Boston and London, Ottimo is strategically positioned to make a significant impact on global cancer research. Medicxi’s backing and the leadership of David Epstein exemplify the strategic investments and expertise driving advancements in oncology. It will be fascinating to see how Jankistomig progresses through its early clinical stages and what it could mean for patients in need of new treatment options. #Biotech #Innovation #Oncology #CancerResearch #DrugDevelopment #BiotechInnovation

85

Excited to share the latest feature in our "Partnering Spotlight" series, where we share some of the connections we are building to foster scientific innovation in healthcare. In this edition, our very own Neha Kaushal sits down with Daniel Anderson, Professor of Chemical Engineering at MIT, to discuss the potential of innovative #mRNA applications in vaccines and novel treatments for genetic diseases. Check out the video to learn more about our collaboration! https://lnkd.in/eHwpyjeY #vaccines #immunoscience

40

1 Comment

Roche's three discontinued MAGE-A4 programs appear to have been based on TCR domain molecules. Could CDR-Life Inc.'s CDR404 - a bispecific and bivalent antibody fragment-based T-cell engager (TCE) targeting MAGE-A4 - yield different results? While antibody-based approaches may exhibit higher affinity for their targets than TCR-based approaches, it's important to note that higher affinity doesn't necessarily translate to improved efficacy. CDR404 is currently undergoing Phase 1 clinical trials (NCT06402201). https://lnkd.in/gQw5ziHF

11

#SABCS24 Following the FDA approval of Inavolisib, SABCS24 will showcase data on various PI3Ka inhibitors. After initial clinical data for RLY-2608 was presented in the September conference call and for STX-478 at ESMO24, updated Phase 1 data for both drugs will be shared at SABCS24. Although the clinical development of LOXO-783 was discontinued, SABCS24 will provide the first opportunity to review its clinical data. Additionally, the preclinical characterization of LY4045004, a new PI3Ka inhibitor being developed based on the lessons learned from the LOXO-783 program, will also be presented. Unlike the previously mentioned mutant-selective PI3Ka inhibitors, preclinical data will also be presented for BBO-10203, a PI3Ka:RAS interaction inhibitor. Recently, BBO-10203 was administered to the first patient in the Phase 1 BREAKER-101 study.

9

Here are some exciting biotech companies in the siRNA (small interfering RNA) space that are advancing innovative therapies through strategic partnerships and recent fundraising rounds. 1. Arrowhead Pharmaceuticals Focus: RNAi therapies for various diseases, with a focus on liver and cardiovascular conditions. Deals: Partnered with Amgen to develop siRNA-based therapies for cardiovascular diseases. They also have agreements with Janssen (Johnson & Johnson) to target hepatitis B and Takeda for non-alcoholic liver diseases. 2. Silence Therapeutics plc Therapeutics Focus: RNAi therapeutics for cardiovascular and metabolic diseases. Deals: Partnered with AstraZeneca to develop siRNA therapies for cardiovascular, renal, and metabolic disorders. Silence also collaborates with Mallinckrodt on RNAi therapies for complement-mediated diseases and has a partnership with Hansoh Bio Pharma to target serious diseases in Asia. 3. Atalanta Therapeutics Focus: siRNA-based therapies for neurodegenerative diseases like Huntington’s and ALS. Deals: Collaborates with Genentech (Roche) to advance siRNA-based therapies for CNS disorders. Their approach aims to unlock new treatments for currently untreatable neurodegenerative diseases. 4. CAMP4 Therapeutics Focus: developing a pipeline of RNA Actuator therapeutic candidates with the potential to open up vast new horizons for patients/ Deals: Recently announced a new research collaboration with BioMarin Pharmaceutical Inc. aimed at advancing novel therapeutics that increase protein levels by targeting regulatory RNA (regRNA) sequences, which are key elements controlling gene expression. The company hhas marked out plans for a $67 million IPO too. 5. Judo Bio Focus: Lead pipeline programs use megalin receptors for intracellular delivery of ligand-siRNA conjugates to specific kidney cells to target and silence genes, including solute carrier proteins. Deals: Judo Bio today announced the company’s launch and $100 million in initial financing, including seed financing and Series A. Atlas Venture founded and incubated Judo Bio with The Column Group joining the seed financing. The Series A was recently closed and co-led by Atlas Venture, TCG and Droia Ventures, with participation from Digitalis Ventures, EUCLIDEAN CAPITAL, LLC Capital, YK Bioventures.

16

"Gilead Sciences continues its divergence out of its original infectious disease beginnings and into cancer and now, more deeply than before, into inflammation, penning a major $1.7 billion deal with dermatology specialist LEO Pharma on the eve of the J.P. Morgan Healthcare conference. The development and commercialization deal zeros in on Leo’s preclinical STAT6 research programs, according to the Jan. 11 release. The transcription factor is used for IL-4 and IL-13 cytokine signaling, a signal found across multiple inflammatory diseases, including eczema, asthma and chronic obstructive pulmonary disease (COPD). Gilead isn't sharing what specific areas it will hone in on—which is not unusual given how early-stage the deal is—but those three disease areas bring in major blockbuster sales for the likes of AbbVie's Skyrizi and Rinvoq, and Sanofi and Regeneron's Dupixent. #Gilead #LeoPharma #STAT6 #transcriptionfactors #inflammation

8

Dr. Nina E. Weisser, Director of Preclinical, Multispecific Antibody Therapeutics, recently authored an article published in Drug Target Review discussing the development of trispecific T cell engagers (TriTCEs) with integrated CD28 costimulation. TriTCEs are designed to address the limitations of conventional bispecific TCEs in treating solid tumors by providing balanced T cell activation, leading to potentially more sustainable anti-tumor responses. This innovative approach could significantly advance immunotherapy for patients with difficult-to-treat solid tumors. Access the article: https://lnkd.in/ewRJvPA9

97

Bristol Myers Squibb (BMS) has shared positive top-line results from two late-stage studies of its oral TYK2 inhibitor Sotyktu (deucravacitinib) in adults with active psoriatic arthritis (PsA). The phase 3 POETYK PsA-1 trial evaluated the drug in patients who were not previously treated with a biologic disease-modifying antirheumatic drug (bDMARD naïve), while POETYK PsA-2 enrolled those who were bDMARD naïve or had previously received TNFα inhibitor treatment. More than eight million people in the US are living with psoriasis, an immune-mediated disease that causes inflammation in the body, and up to 30% will develop PsA, which is characterised by joint pain, stiffness and swelling. Both trials met their primary endpoint, with a significantly greater proportion of Sotyktu-treated patients achieving at least a 20% improvement in the signs and symptoms of the disease compared to placebo after 16 weeks of treatment. Important secondary endpoints across PsA disease activity at week 16 were also met in both trials, BMS said, adding that the overall safety profile of Sotyktu with the established safety profile of the drug. Roland Chen, senior vice president and head, immunology, cardiovascular and neuroscience development, BMS, said the findings “demonstrate that oral Sotyktu has the potential to be the first TYK2 inhibitor for people living with PsA”. “We are encouraged by the positive data across both phase 3 trials and look forward to discussing the results with health authorities,” he said. Sotyktu is already approved in major markets to treat certain patients with moderate-to-severe plaque psoriasis after being shown in late-stage trials to improve skin clearance, symptom burden and quality of life. BMS also recently shared positive results from the phase 3b/4 PSORIATYK SCALP study of Sotyktu in moderate-to-severe scalp psoriasis. Read more: https://lnkd.in/eMV6dhHX Stay in touch with all the leading stories, events and opportunities by subscribing to my weekly LinkedIn Newsletter here:  https://bit.ly/3KQs0mD

1

For those interested in Physiologically Based Biopharmaceutics Modeling (PBBM) please check out our recently published article from the 2023 PBBM workshop. It proposes best practices for measuring solubility, dissolution, precipitation and permeability for parameterizing PBBMs, summarizes breakout sessions, and shares PBBM case studies. https://lnkd.in/gda_HH4F

95

2 Comments

Bristol Myers Squibb has queued a Phase 1 study of Orum Therapeutics’ ORM-6151 (BMS-986497), a first-in-class, anti-CD33 antibody-enabled GSPT1 degrader for the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndromes. The study will enroll an estimated 35 patients and is due to start in late May 2024. Orum Therapeutics has developed a new class of ADC payloads, called neoDegraders, to specifically degrade intracellular target proteins within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, neoDegraders are designed to be delivered specifically to cancer cells and degrade the intracellular target protein and cause tumor cell death. https://lnkd.in/edTcDRFj

32

Let’s hope this is a big step forward by anticipating and addressing potential regulatory backlog given the inflection of #cellandgene therapy and #AI approaches. The logic being that a standardized framework for development platforms could take less assessment time and offer #biotech swifter approvals and reduced development costs. #innovation #medicine #pharmaceutical #

5

𝐁𝐫𝐢𝐬𝐭𝐨𝐥 𝐌𝐲𝐞𝐫𝐬 𝐒𝐪𝐮𝐢𝐛𝐛 𝐀𝐧𝐧𝐨𝐮𝐧𝐜𝐞𝐬 𝐏𝐨𝐬𝐢𝐭𝐢𝐯𝐞 𝐓𝐨𝐩𝐥𝐢𝐧𝐞 𝐑𝐞𝐬𝐮𝐥𝐭𝐬 𝐟𝐫𝐨𝐦 𝐓𝐰𝐨 𝐏𝐢𝐯𝐨𝐭𝐚𝐥 𝐏𝐡𝐚𝐬𝐞 𝟑 𝐓𝐫𝐢𝐚𝐥𝐬 𝐄𝐯𝐚𝐥𝐮𝐚𝐭𝐢𝐧𝐠 𝐒𝐨𝐭𝐲𝐤𝐭𝐮 (𝐝𝐞𝐮𝐜𝐫𝐚𝐯𝐚𝐜𝐢𝐭𝐢𝐧𝐢𝐛) 𝐢𝐧 𝐀𝐝𝐮𝐥𝐭𝐬 𝐰𝐢𝐭𝐡 𝐏𝐬𝐨𝐫𝐢𝐚𝐭𝐢𝐜 𝐀𝐫𝐭𝐡𝐫𝐢𝐭𝐢𝐬 Bristol Myers Squibb (NYSE: BMY) Bristol Myers Squibb today announced results from POETYK PsA-1 (IM011-054) and POETYK PsA-2 (IM011-055), the pivotal Phase 3 trials evaluating the efficacy and safety of Sotyktu (deucravacitinib) in adults with active psoriatic arthritis (PsA). Both trials met their primary endpoint, with a significantly greater proportion of Sotyktu-treated patients achieving ACR20 response (at least a 20 percent improvement in signs and symptoms of disease) after 16 weeks of treatment compared with placebo. $BMY announced topline results from two pivotal Phase 3 studies for an investigational treatment in adults with #PsoriaticArthritis. Additionally, the POETYK PsA-1 and POETYK PsA-2 trials met important secondary endpoints across PsA disease activity at Week 16. The overall safety profile of Sotyktu through 16 weeks of treatment in the POETYK PsA-1 and POETYK PsA-2 trials was consistent with the established safety profile of Sotyktu observed in a Phase 2 PsA clinical trial and Phase 3 moderate-to-severe plaque psoriasis clinical trials. "Psoriatic arthritis is a heterogeneous disease that causes a range of symptoms, including joint pain and swelling, as well as psoriatic skin lesions. Despite available therapies, rheumatologists continue to express a need for a safe and effective oral treatment," said Roland Chen, MD, senior vice president and head, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb. "These POETYK PsA-1 and POETYK PsA-2 findings demonstrate that oral Sotyktu has the potential to be the first TYK2 inhibitor for people living with psoriatic arthritis and reinforce the established efficacy and safety profile of Sotyktu. We are encouraged by the positive data across both Phase 3 trials and look forward to discussing the results with health authorities." Bristol Myers Squibb will work with key investigators to present detailed results at upcoming medical congresses. These topline results represent the first Phase 3 clinical trials for Sotyktu in a rheumatic condition. Sotyktu is approved in numerous countries around the world for the treatment of adults with moderate-to-severe plaque psoriasis. Bristol Myers Squibb thanks the patients, investigators, and clinical trial sites who participated in these clinical trials. #PsoriaticArthritis #PsA #Sotyktu #Deucravacitinib #Immunology #Rheumatology #BristolMyersSquibb #Phase3Trials #AutoimmuneDisease #Psoriasis #AR20Response #TYK2Inhibitor

Latest on MDMA rejection; Novo vs. Lilly earnings; Recursion, Exscientia to merge; Q&A with Genentech CEO; and more https://lnkd.in/gRuf3XRp Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up [...] #LosAngeles #OrangeCountyCA #Biotech #Lifescience #News

1

🔬 Biopharma Layoffs: Navigating Challenges in a Shifting Landscape Recent trends in biopharma layoffs have left many scientists reeling. Here are key takeaways from a recent STAT article: 67% of life science layoffs in H1 2024 were at large biopharma companies (>$1B annual sales), up from 47% in 2021-2023. Job postings in biotech dropped from 21,366 to 12,300 between early 2021 and 2024. Scientists face unique challenges in job searches, including maintaining confidentiality about previous work. Visa constraints add pressure for international workers, limiting job search time. Networking remains crucial: Some successful companies are hiring primarily through personal connections. The industry sees this as part of a cyclical pattern, influenced by patent expirations and acquisitions. Despite these challenges, opportunities still exist. Adaptability, networking, and a broader job search approach are key for scientists navigating this evolving landscape. What strategies have you found effective in weathering industry changes? Share your thoughts below! #BiopharmaJobs #CareerTransition #LifeSciences #Networking

3