The Biotech Beat: 8.5-8.11.24

by Joey Bose and Aruesha Srivastava

🌟Upshot

💉 The biotech industry is at a pivotal moment, with major players like Eli Lilly, Novo Nordisk, and Merck making bold moves that could reshape the future of medicine. 📈 Eli Lilly has raised its full-year revenue guidance by $3 billion, driven by the explosive growth of its GLP-1 drugs, Mounjaro and Zepbound, which now contribute nearly 40% of the company's revenue. Meanwhile, 🛑 Novo Nordisk is fiercely defending its market dominance by filing 11 new lawsuits against compounding pharmacies producing unauthorized versions of its blockbuster semaglutide products. 💰 Merck, not to be outdone, is making a $700 million bet on CD3xCD19 bispecifics in collaboration with Daiichi Sankyo, while also navigating challenges with supply chain management and competition in the obesity drug market. 🔗 At the same time, the industry is witnessing a surge in innovative partnerships, like Eisai’s $1.5 billion deal with SEED Therapeutics for molecular glue therapies, and a wave of venture capital investments, with TPG closing a $580 million fund targeting life sciences startups. 🚀

🔬 Research, Development & Drug Approvals 💊

🧬 Avidity's DMD Breakthrough: A Game-Changer in a Troubled Field

The Facts

Avidity Biosciences has reported unexpectedly positive early Phase 1/2 results for its RNA therapy, delpacibart zotadirsen (del-zota), aimed at treating Duchenne muscular dystrophy (DMD). The RNA drug increased dystrophin levels—a critical protein for muscle function—by 25%, surpassing expectations by reaching 32% of normal dystrophin levels in DMD patients. This promising outcome, achieved in a study targeting patients with exon 44 mutations, has set Avidity on a fast track to seek accelerated FDA approval. Despite some adverse events, including a serious case of anaphylaxis, the company’s stock surged by 13%, continuing a remarkable year-to-date increase of over 360%.

Our Opinion

Avidity's success is a beacon of hope in the otherwise grim landscape of DMD treatment development, especially after high-profile failures from Pfizer and Sarepta Therapeutics. While the results are encouraging, it's critical to question whether the early excitement will hold up in larger, more diverse patient populations. The biotech industry must remain vigilant about the balance between accelerated approvals and thorough vetting, particularly in the high-stakes realm of rare diseases.

Your Turn

How might Avidity Biosciences' approach to RNA therapy for DMD impact the broader landscape of treatments for genetic muscle disorders, and what lessons can be learned from the failures of other late-stage programs in this field?

💰 Novartis' Fabhalta: Life-Saving or Price-Gouging in Autoimmune Kidney Disease?

The Facts

Novartis has secured FDA accelerated approval for Fabhalta, its treatment for IgA nephropathy, a severe autoimmune kidney disease. Fabhalta, which previously gained approval for a rare blood disorder, PNH, is priced at $550,000 per year—far higher than existing therapies for IgA nephropathy, which range between $120,000 and $180,000 annually. Despite this steep cost, Novartis justifies the price by comparing it to other complement inhibitors. The approval was granted based on data showing a significant reduction in antibody buildup in patients' urine, with Novartis now working to provide confirmatory evidence that Fabhalta can slow kidney function decline.

Our Opinion

While Fabhalta's approval is a significant milestone in the fight against IgA nephropathy, the staggering price tag raises ethical questions about the affordability and accessibility of such treatments. The biotech industry must grapple with the balance between innovation and the potential exploitation of patients in dire need. Novartis' ambition to market Fabhalta across multiple rare diseases could either represent a revolutionary "pipeline-in-a-product" or a worrisome trend in drug pricing that could limit access to life-saving treatments.

Your Turn

How should the healthcare system address the ethical challenges posed by the high costs of breakthrough treatments like Fabhalta, especially when comparable therapies are available at significantly lower prices?

🎯 Lilly’s Alzheimer’s Hope Fades as Tau-Targeting Drug Fails Phase 2 Trial

The Facts

Eli Lilly, fresh off the approval of its Alzheimer’s drug donanemab, faces a significant setback with the failure of its tau-targeting therapy, LY3372689, in a Phase 2 trial. The drug, an O-GlcNAcase inhibitor, failed to achieve its primary endpoint of reducing Alzheimer’s severity, casting doubt on tau as the next frontier in Alzheimer’s treatment. Despite this disappointment, Lilly remains committed to exploring tau biology, with other Alzheimer’s therapies in various stages of development. Additionally, Lilly has quietly halted several other programs, including a mutant-selective PI3Kα inhibitor for breast cancer and a GITR antagonist for immunology, due to insufficient efficacy.

Our Opinion

Lilly’s recent failure highlights the harsh realities of Alzheimer’s drug development, where even the most promising targets can falter in clinical trials. While the company’s commitment to advancing Alzheimer’s research is commendable, this setback raises questions about the feasibility of tau-targeted therapies and the broader strategy of pursuing multiple experimental approaches simultaneously. Investors and researchers alike must remain cautious, as the path to effective Alzheimer’s treatments continues to be fraught with challenges, despite the occasional triumph.

Your Turn

Given the failure of Lilly’s tau-targeting drug, how should pharmaceutical companies balance the pursuit of innovative but risky Alzheimer’s treatments with the need for steady progress in addressing this complex disease?

🧠 Liraglutide's Surprising Alzheimer's Comeback: A Missed Opportunity or a Glimpse of Hope?

The Facts

Novo Nordisk's GLP-1 drug, liraglutide, which was overshadowed by its successor Ozempic, has shown promise in a small Phase 2 trial for mild Alzheimer’s disease. While the trial did not meet its primary endpoint of altering glucose metabolism in the brain, it succeeded in secondary measures, reducing brain volume loss by nearly 50% and slowing cognitive decline by 18%. The study, which involved 204 patients over a year, suggests that liraglutide may protect the brain similarly to how statins protect the heart, despite its main use as a diabetes and weight loss treatment.

Our Opinion

Liraglutide’s unexpected success in slowing cognitive decline raises intriguing possibilities for repurposing older drugs, but it also highlights the complexities and challenges in Alzheimer’s drug development. Novo Nordisk’s focus on newer drugs like Ozempic may mean liraglutide won't get the attention it deserves, potentially leaving a valuable treatment underutilized. The biotech industry must weigh the benefits of pursuing multiple avenues for Alzheimer's treatment against the risk of sidelining promising therapies due to market pressures and newer, flashier drugs.

Your Turn

How can pharmaceutical companies ensure that potentially effective treatments like liraglutide are not overlooked in favor of newer drugs, especially when they show promise in complex diseases like Alzheimer’s?

🧠 Vorasidenib: A Pricey New Hope in the Battle Against Rare Brain Cancer

The Facts

The FDA has granted approval to Servier Pharmaceuticals' vorasidenib, now branded as Voranigo, as a treatment for grade 2 astrocytoma or oligodendroglioma with IDH1 or IDH2 mutations. Priced at $39,881 per month, Voranigo offers a groundbreaking option for a rare and challenging form of brain cancer, extending progression-free survival by an average of 16.6 months compared to placebo. This approval marks a significant leap forward for a disease that has seen little progress in over two decades. Vorasidenib’s ability to cross the blood-brain barrier, a major hurdle in brain cancer treatment, underscores its potential to alter the landscape of care for the approximately 3,000 patients diagnosed annually in the US.

Our Opinion

While vorasidenib represents a monumental advance in treating IDH-mutant brain tumors, its exorbitant cost raises critical concerns about accessibility and the broader implications for healthcare systems. The steep price tag, set at nearly $40,000 per month, highlights the ongoing tension between innovation and affordability in the biotech industry. As life-saving treatments like Voranigo emerge, the challenge remains to ensure that such breakthroughs are not limited to those who can afford them, but are made accessible to all who need them.

Your Turn

How can healthcare systems and insurers balance the high cost of cutting-edge treatments like Voranigo with the need to provide access to life-saving therapies for all patients, particularly in the context of rare diseases?

🍄 FDA Rejection Shakes Lykos’ MDMA-Assisted PTSD Treatment: Setback or a Necessary Rethink?

The Facts

Lykos' ambitious journey to bring MDMA-assisted therapy for PTSD to market hit a major roadblock as the FDA rejected its application, demanding an additional Phase 3 study. Despite over two decades of research, the FDA's decision, influenced by an advisory committee’s concerns over trial integrity and data reliability, has put the future of this potentially groundbreaking treatment in jeopardy. Lykos CEO Amy Emerson expressed deep disappointment, but the company's ability to move forward remains uncertain, especially with financial resources already strained.

Our Opinion

This rejection highlights the complex and often contentious path of translating psychedelics into approved medical treatments. While the potential of MDMA-assisted therapy to revolutionize PTSD treatment is enormous, the FDA’s insistence on more rigorous evidence underscores the critical need for robustness and transparency in clinical trials, especially for treatments that carry significant ethical and safety concerns. Lykos must now navigate the challenging terrain of securing additional funding and addressing the FDA’s critiques, all while maintaining the support of a patient community that is desperate for new options.

Your Turn

Given the FDA’s concerns and the mixed data from Lykos’ trials, what steps should the company take to ensure the success and credibility of an additional Phase 3 study, especially in the context of the broader psychedelic research movement?

🧬 Tecelra: A Revolutionary Yet Pricey Leap in Rare Cancer Treatment

The Facts

The FDA has granted accelerated approval to Adaptimmune Therapeutics' Tecelra (afami-cel), the first T cell receptor-based cell therapy for synovial sarcoma, a rare and aggressive form of cancer. Tecelra is designed for patients with metastatic or inoperable tumors that express the MAGE-A4 protein and possess the HLA-A*02 marker, making it a highly personalized treatment option. With a list price of $727,000 per patient, Tecelra is even more expensive than CAR-T therapies, reflecting its cutting-edge nature. The therapy demonstrated a 39% tumor reduction rate in a Phase 2 trial, though it comes with significant risks, including a 71% rate of cytokine release syndrome.

Our Opinion

While Tecelra represents a groundbreaking advance in the treatment of solid tumors, its exorbitant cost and the limited eligibility based on specific genetic markers raise serious concerns about accessibility and equity. The fact that Tecelra’s eligibility criteria disproportionately favor the Caucasian population highlights a broader issue in the development of precision medicines: the risk of widening health disparities. As the biotech industry celebrates this milestone, it must also critically address the ethical implications of who gets to benefit from these expensive and exclusive treatments.

Your Turn

How can the biotech industry ensure that the development of personalized therapies like Tecelra does not exacerbate existing health disparities, particularly in the context of rare and aggressive diseases?

💰 Investment, M&A, and IPOs 📈

💉 Merck’s $700M Gamble: A New Contender in the Blood Cancer and Autoimmune Arena

The Facts

Merck & Co. has made a bold move by investing $700 million upfront to secure global rights to Curon Biopharmaceutical’s CD3xCD19 bispecific antibody, CN201, positioning itself as a direct rival to Amgen and AstraZeneca in the blood cancer market. CN201 has shown early promise in Phase 1/2 trials for non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL), where it elicited complete responses in heavily pretreated patients. With the potential to reduce cytokine release syndrome (CRS) without sacrificing efficacy, CN201 could challenge Amgen’s pioneering Blincyto, which has dominated the market since its 2014 FDA approval. Merck is also eyeing the autoimmune disease market, where CD19 targeting has shown dramatic results in lupus and rheumatoid arthritis.

Our Opinion

Merck’s hefty upfront payment and commitment to further milestones signal its high-stakes entry into a fiercely competitive market. While the early results for CN201 are encouraging, Merck’s bet hinges on overcoming the entrenched position of Blincyto and proving the broader applicability of CD19 targeting in autoimmune diseases. The pressure is on to deliver not just a competitor but a superior option in both oncology and autoimmune conditions, where efficacy, safety, and scalability will be key determinants of success.

Your Turn

How might Merck's strategic investment in CD3xCD19 bispecific antibodies reshape the competitive landscape in both oncology and autoimmune diseases, and what challenges could the company face in displacing established therapies like Blincyto?

🤖 AI Drug Development Giants Merge: Can Recursion and Exscientia Revolutionize Biotech Together?

The Facts

In a landmark deal for the AI-driven drug development sector, Recursion Pharmaceuticals and Exscientia are merging in a $688 million all-stock transaction. The combined entity will retain the Recursion name, with Recursion co-founder Chris Gibson at the helm. This merger, one of the first major consolidations in the burgeoning AI drug development space, creates a powerhouse with 10 clinical-stage drug readouts expected over the next 18 months and partnerships with pharma giants like Roche-Genentech, Sanofi, and Bayer. Despite Exscientia's recent setbacks, including laying off a quarter of its staff, the merger positions the new company to potentially transform the inefficient and failure-prone drug development process using cutting-edge AI and machine learning tools.

Our Opinion

This merger underscores the growing importance of AI in biotech, but it also raises questions about whether combining two companies with different trajectories can truly accelerate drug discovery or simply lead to more growing pains. While the promise of AI to revolutionize drug development is enormous, success hinges on the new Recursion's ability to integrate technologies and pipelines efficiently. The industry will be watching closely to see if this merger lives up to its hype or if it will struggle under the weight of its ambitious goals.

Your Turn

With the merger of Recursion and Exscientia, what are the key challenges the combined company must overcome to prove that AI can truly revolutionize the drug development process, and how might their success or failure impact the broader biotech industry?

💥 Daiichi Sankyo and Merck Double Down on T Cell Engagers: A High-Stakes Bet in Lung Cancer Treatment

The Facts

Daiichi Sankyo is investing $170 million upfront to secure joint development and commercialization rights to Merck's Phase 1/2 T cell engager, MK-6070, expanding their already significant partnership. This move follows Merck's acquisition of the drug earlier this year through Harpoon, and it deepens the collaboration between the two pharmaceutical giants, which already includes three antibody-drug conjugates. MK-6070, currently in early-stage trials as a monotherapy and in combination with Roche’s Tecentriq, targets DLL3 and is aimed at tackling the aggressive small cell lung cancer (SCLC) market, where new treatments are desperately needed.

Our Opinion

This deal reflects the growing trend of pharmaceutical companies doubling down on next-generation cancer therapies, but it also highlights the risks involved in such high-stakes partnerships. With the recent FDA rejection of a lead antibody-drug conjugate from the duo's earlier collaboration, the success of MK-6070 becomes even more critical. If this venture succeeds, it could pave the way for novel combination therapies that address the urgent needs of SCLC patients, but failure could cast doubt on the viability of T cell engagers in this challenging oncology space.

Your Turn

Given the competitive landscape and the recent setbacks in their joint ADC development, how can Merck and Daiichi Sankyo leverage their partnership to maximize the chances of success for MK-6070 in the treatment of small cell lung cancer?

💸 Life Science VC Fundraising Hits Record Low: Is Biotech's Future in Jeopardy?

The Facts

The life science venture capital industry is on track for another record-low year in fundraising, with only 15 funds raised in the first half of the year compared to 53 in 2022. This sharp decline could significantly impact the availability of capital for biotech startups in the coming years. The slowdown is attributed to the post-Covid market correction, where overinflated startup valuations and a lackluster biotech stock market have left many VC firms struggling. Despite these challenges, some firms like Flagship Pioneering have managed to raise substantial funds, thanks to their focus on emerging technologies like AI, which has captivated investors' interest.

Our Opinion

This downturn in VC fundraising presents a critical challenge for the biotech industry, potentially stifling innovation and slowing the pace of new drug development. While firms like Flagship Pioneering may thrive due to their unique model and AI-driven focus, the broader industry could face a funding drought that limits opportunities for groundbreaking startups. The biotech sector must navigate this challenging financial landscape with caution, balancing the need for innovation with the realities of reduced capital flow.

Your Turn

How can biotech startups adapt to the current financial environment with reduced access to venture capital, and what strategies should they employ to secure the necessary funding for their innovations?

💼 TPG’s $580M Life Sciences Fund: A Beacon of Hope Amid VC Funding Decline?

The Facts

TPG has announced the closing of a $580 million "Life Sciences Innovations" fund, marking another significant push into biotech and life sciences by large asset managers. The fund, which aims to invest in 15 to 20 companies, joins the ranks of similarly large funds from Goldman Sachs and JP Morgan, highlighting a continued appetite for life sciences despite broader venture capital fundraising challenges. TPG, which manages $229 billion in assets, has already begun deploying capital into promising biotech startups such as MBrace Therapeutics and Santa Ana Bio, with a focus on preclinical and clinical-stage therapeutics across various therapeutic areas, including oncology and rare diseases.

Our Opinion

TPG's substantial fund underscores the resilience and potential of the life sciences sector, even as venture capital struggles with a funding downturn. The involvement of seasoned leaders with deep expertise in the biotech space signals a strong commitment to advancing innovative therapies. However, the fund’s success will depend on its ability to identify and nurture truly groundbreaking startups in a market that has become increasingly selective. This influx of capital is a welcome development, but it also raises the stakes for biotech companies to deliver on their promises.

Your Turn

In light of the recent challenges in venture capital fundraising, how might large funds like TPG's "Life Sciences Innovations" shape the future of biotech startup investments, and what strategies should these startups adopt to attract attention from such sizable investors?

🧬 Eisai Bets Big on Molecular Glue with $1.5B SEED Therapeutics Deal: A New Frontier in Neurodegeneration and Cancer?

The Facts

Eisai has inked a deal worth up to $1.5 billion with SEED Therapeutics to develop innovative "molecular glue" therapies for neurodegenerative diseases and cancer. While the upfront payment remains undisclosed, the collaboration marks a significant expansion in Eisai's portfolio, leveraging SEED's expertise in molecular glues—a novel drug modality that directs disease-causing proteins to the body’s natural protein degradation pathways. This partnership builds on SEED’s growing reputation, following a $24 million Series A-3 funding round led by Eisai, and adds to SEED’s existing pharma partnerships, including a notable deal with Eli Lilly.

Our Opinion

Eisai's ambitious move into the molecular glue space signals a broader shift in the pharmaceutical industry towards targeting the root causes of diseases at a molecular level. However, while the potential is enormous, the challenge lies in translating these early-stage technologies into viable therapies for complex conditions like neurodegeneration and cancer. With competitors like Takeda also entering the molecular glue arena, the race is on to see who can unlock the full therapeutic potential of this groundbreaking approach.

Your Turn

Given the early-stage nature of molecular glue technology, what strategies should Eisai and SEED Therapeutics employ to maximize the chances of success in developing effective treatments for neurodegenerative diseases and cancer?

⚖️ Politics & Policy 🏛️

🔬 Eli Lilly’s Obesity Drug Success: Triumph or Ticking Time Bomb?

The Facts

Eli Lilly's recent financial success, driven primarily by its GLP-1 weight loss drugs, paints a rosy picture, but the company’s top scientist warns of the challenges ahead in sustaining this momentum. Despite dominating the obesity market and making up nearly 50% of the quarter’s revenue, Lilly faces stiff competition from emerging rivals and the daunting task of scaling manufacturing to meet soaring demand. While Lilly has invested billions into expanding production and securing label expansions, Chief Scientific Officer Dan Skovronsky cautions that developing new, competitive molecules in this space remains fraught with difficulty.

Our Opinion

Lilly’s triumph in the obesity market underscores both the potential and the peril of the biotech industry’s latest frontier. The company’s aggressive investment in manufacturing and legal battles against compounders reflects a relentless pursuit of market dominance. However, the cautionary notes from its leadership signal that the road ahead is far from guaranteed. The real test will be whether Lilly can maintain its lead in the face of increasing competition and whether it can balance innovation with the practical challenges of mass production and market saturation.

Your Turn

With new competitors entering the obesity drug market and Lilly’s challenges in scaling production, how should the company strategize to maintain its market dominance while addressing potential supply chain vulnerabilities and legal challenges?

⚠️ The Dark Side of Online Pharmacies: Dangerous Counterfeits and Compounded GLP-1s on the Rise

The Facts

As shortages of GLP-1 obesity and diabetes medications continue, a disturbing trend has emerged: patients are increasingly turning to illegal online pharmacies and compounded versions of these drugs, risking their health in the process. A new study published in JAMA Network Open reveals that semaglutide purchased from illegal sites often contains significantly more of the drug than labeled, with one sample even showing signs of bacterial contamination. The FDA has issued warnings about the dangers of compounded GLP-1s, citing severe adverse events like dosing errors leading to hospitalization. The rise of counterfeit drugs and unregulated compounded versions highlights the growing risks patients face as they seek alternatives amid supply shortages.

Our Opinion

The findings from this study underscore the critical dangers of unregulated online drug purchases, where the risks of contamination, incorrect dosing, and outright scams are alarmingly high. While patients are desperate for access to these life-changing medications, the lack of oversight in online pharmacies and compounding practices poses a severe threat to public health. As branded GLP-1 drugs become more available, the industry must take urgent steps to curb the proliferation of these dangerous alternatives. Until then, the onus is on both healthcare providers and patients to ensure that medications are sourced from legitimate, FDA-approved pharmacies.

Your Turn

How should regulatory bodies and healthcare providers address the rising trend of patients turning to illegal online pharmacies and compounded drugs due to medication shortages, and what measures can be implemented to protect consumers from these dangerous alternatives?

💹 Eli Lilly’s $3 Billion Boost: The GLP-1 Juggernaut Propels Pharma Giant to New Heights

The Facts

Eli Lilly has raised its full-year revenue guidance by an impressive $3 billion, thanks to surging sales of its GLP-1-based diabetes and obesity drugs, Mounjaro and Zepbound. The company now forecasts 2024 sales between $45.4 billion and $46.6 billion, a significant increase from its previous estimate. In the second quarter alone, Lilly reported $11.3 billion in revenue, outpacing analyst expectations, with Mounjaro and Zepbound contributing nearly 40% of the total. Despite earlier supply shortages, Lilly’s GLP-1 business is thriving, reflecting robust demand and a strong market position that has led to a 7% surge in the company’s shares.

Our Opinion

Lilly’s remarkable performance underscores the massive potential of GLP-1 drugs in the pharmaceutical market, yet it also highlights the challenges of meeting skyrocketing demand. While the company’s financials are booming, the continued risk of supply bottlenecks could temper future growth if not managed effectively. As Lilly expands its GLP-1 pipeline and navigates the complexities of large-scale production, it must balance investor expectations with the practical realities of sustaining supply for a product line that has quickly become central to its revenue stream.

Your Turn

How can Eli Lilly strategically manage its supply chain to maintain the momentum of its GLP-1 business while addressing potential production challenges and staying ahead of emerging competition in the obesity and diabetes markets?

🛑 Novo Nordisk’s Legal Blitz: Cracking Down on Compounded Semaglutide to Protect Market Dominance

The Facts

Novo Nordisk is intensifying its legal campaign against compounding pharmacies and businesses that are producing and marketing unauthorized versions of its blockbuster semaglutide products for diabetes and weight loss. The company recently filed 11 new lawsuits across seven states, bringing its total legal actions to 34, with six already resulting in permanent injunctions. Novo Nordisk’s aggressive stance is aimed at curbing what it describes as false and misleading marketing practices that deceive patients into believing they are purchasing legitimate, FDA-approved products. This move aligns with similar efforts by its rival, Eli Lilly, as both companies seek to protect their market share from the surge of compounded GLP-1 offerings.

Our Opinion

Novo Nordisk’s crackdown highlights the growing tension between pharmaceutical giants and the expanding world of compounded medications. While the company’s legal actions are framed as a commitment to patient safety, they also reflect the fierce competition in the booming weight loss drug market. As compounded versions of semaglutide gain popularity, Novo Nordisk's efforts to shut down these alternatives could be seen as an attempt to stifle competition and maintain its lucrative market position. However, this strategy may also backfire if patients perceive it as limiting access to more affordable or accessible treatment options.

Your Turn

How might Novo Nordisk’s aggressive legal strategy against compounding pharmacies impact patient access to semaglutide treatments, and what ethical considerations should be taken into account as the company seeks to protect its market share?

If you enjoyed this article, be sure to subscribe and follow Joey Bose!

Disclaimer: The contents of this article are not to be construed with investment advice. The information presented in this article is a compilation of current events, technical analyses, corporate press releases, and the author's personal viewpoints about the biotechnology industry. While efforts have been made to provide accurate and timely information, there may be inadvertent errors, omissions, or inaccuracies. Therefore, investment decisions should not be made solely based on the content of this article. The article may contain statements that are forward-looking in nature, encompassing predictions and future expectations that are subject to inherent risks and uncertainties; as such, actual outcomes may significantly deviate from those expressed or implied herein. This article serves purely as an informational and entertainment resource, and should not be construed as an endorsement to purchase or sell any financial securities. Prior to engaging in any investment activities, it is imperative that you conduct comprehensive due diligence and consult with a qualified financial advisor.