【年会总结】2024 BioSpark Annual Conference Summary

Keynote 1: Neurobiological mechanisms of ASD: from genes to circuits

Dr. Guoping Feng, Poitras Chair Professor of Neuroscience @ MIT and member of National Academy of Sciences, introduced synaptic dysfunction as a converging mechanism of Autism Spectrum Disorder (ASD). The Feng lab has a focus on the postsynaptic complex. Dr. Feng first introduced a monogenic form of ASD caused by SHANK3 mutations, presented results from AAV gene therapy in SHANK3 animal models.  Dr. Feng then introduced sporadic forms of ASD, comprising over 75% ASD patient population, and proposed circuit function modulation as a therapeutic approach for this form of ASD. In particular, NR2B antagonists showed promising results in mice models.

Keynote 2: Cancer Immunotherapy

Dr. Gordan Freeman, professor of Medicine @ Dana-Farber Cancer Institute and Harvard Medical School, first gave us a historical overview of PD-L1/PD-1. He then pointed out that only 30-40% of solid tumor patients would benefit from PD-1/PD-L1 therapy and pointed towards combination therapy as a strategy to benefit more cancer patients. Next, he revealed exciting new research focusing on PD-L2/RGMb interaction and gut microbiota as a candidate resistant mechanism to PD-1/PD-L1 cancer therapy. As a final note, Dr. Freeman showed KIR3DL3-HHLA2 interaction as a new immune checkpoint target that is complementary to PD-1/PD-L1 therapy.

Keynote 3: AI for genomic medicine: disease circuitry, patient heterogeneity, therapeutic design

Dr. Manolis Kellis, Professor of Computer Science and Artificial Intelligence @ MIT and Broad Institute, gave an overview of recent advances in disease phenotyping, genetics and single cell ‘omics. He highlighted major paradigm shifts in data, genomes and AI. He gave several specific examples on FTO genetic region in treating obesity, APOE, cholesterol transport in treating Alzheimer’s Disease, astrocytes’ function in cognitive resilience and single cell insights in schizophrenia. At the end of the talk, he showcased the power of AI in embedding knowledge and providing a map for researchers to speed up drug development.

Dr. Jun Wang shared his personal journey of 20 years in the field of immuno-oncology (I/O) witnessing the rise of PD-1 immunotherapy. For the annual review in oncology, he highlighted the approval of first T cell engager (Amgen’s DLL3/CD3) in solid tumor, IL15 (ImmunityBio) as the 3rd cytokine approved for cancer, the approval of first TIL therapy (Iovance) and the PD-L1/VEGF bispecific antibody success in the past year. He also highlighted several significant setbacks in TIGIT and CD47.  For the annual review in autoimmune diseases, he highlighted the excitement for Th2 cytokines blockade, TL1A deals in inflammatory bowel disease (IBD) and B cell targeted therapies. 

Dr. Lihua Yu highlighted the success of several synthetic lethal oncology targets, PRMT5 and WRN, in the past year. She also mentioned the success of first pan-RAS inhibitors bringing new hope for patients with KRAS mutations. Next generation of AR PROTAC degraders also showed better efficacy in prostate cancer patients compared with predecessors. In the end, she discussed the success and failures of TROP2 ADC trails.

Dr. Avery (Qinghong) Yan introduced session 3 by giving a high-level overview of the RNA field, Pros & Cons of different modalities, and the market performance all the approved RNA drugs. She then reviewed news in the RNA field in each month over the past year. 

Dr. Leon Tang gave an annual review on Biotech business news and an overview of the M&As in the past recent years in Biotech industries. He also showed the big biotechs and pharmaceuticals in China.

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The distinguished panel first reflected current precision oncology approaches, highlighting target druggabilities, drug resistance, safety and biomarker strategies. The group then discussed topics of combination therapy, early detection, immune system diversity and translation challenges of preclinical studies. Next, the group brainstormed on new approaches on the horizon, discussing advancements in the fields of molecular profiling, AI/ML, antibody design and cell therapies. To wrap up, the group discussed precision medicine beyond oncology, including topics of differentiating sporadic and monogenic forms of diseases, new improvements of designing agonists, understanding of polygenic diseases and AI/ML approaches of redefining disease phenotypes.

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To kick off the discussion in session 3, each panelist provided a brief introduction about their companies, technologies, and programs. Following these introductions, Avery invited the panelists to share the latest advances and exciting progress within their companies, accompanied by follow-up questions.

Dr. Isabell Aznarez discussed the disease areas that Stoke Therapeutics is focusing on, using ASOs to restore protein levels. She highlighted the challenge of selecting the right target, noting that if the correct target is identified, the drug is likely to be successful. She emphasized the importance of tissue delivery and discussed the dual aspects of ASOs, which can benefit patients but also have potential side effects. She cited SPINRAZA® (nusinersen), a drug that treats SMA in children and adults, as an example. In summary, Dr. Aznarez mentioned that Stoke is continually expanding and seeking new technologies rather than limiting itself to current ones.

Dr. Paul Nioi shared Alnylam’s siRNA programs and CNS delivery technology. He observed that Alnylam’s pipeline is diversifying and excitingly announced that multiple new therapeutic areas and pipelines will be launched by 2025. The company aims to administer the first dose to patients suffering from Huntington’s disease by 2025.

Mr. Jay Stella discussed the two platforms that Strand Therapeutics has developed and the next generation of programmable mRNA technology. He provided examples of recent developments in the field of RNA therapeutics. Jay believes that two of the most critical factors for a successful drug are the ability to manufacture the drug at very high purity and generating compelling clinical data.

Dr. Simon Xi from Rgenta Therapeutics shared his professional experiences and observations. He mentioned that RNA is easy to target with small molecules and can be used in many neuroscience disease areas like Alzheimer’s and Huntington’s diseases. However, the challenge lies in targeting RNA due to its dynamic nature and the complexity added by thousands of available proteins. Rgenta Therapeutics is focusing on correcting gene splicing to help treat diseases like Alzheimer’s.

Dr. Kasper Roet from QurAlis shared how he co-founded the company with the goal of helping patients suffering from life-shortening diseases. QurAlis currently has three programs targeting ALS. He mentioned that for a startup like QurAlis to survive, sustain, and expand, it needs to focus on two pillars: financials and R&D. Dr. Roet is confident about QurAlis’ programs and  outcomes as they understand the muscle loss in ALS patients and aim to treat it effectively.

As a closing remark for session 3, Avery asked the panelists about outlook of RNA therapeutics in the future. Isabell expressed her belief that there are no limitations to RNA targeting and mentioned that AI could be helpful in this area. Jay discussed the potential of RNA therapeutics companies to explore an RNA-based approach to in vivo editing across a range of therapeutic areas. Simon emphasized the importance of understanding diseases and enrolling the right patients in clinical trials.

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In session 4, Leon Tang moderating a panel discussion on "Business Partnership and Collaboration." The distinguished panelists included Chong Xu, Ph.D., a partner at F-Prime Capital; Erica Wang, Esq., founder of Veritas Law; John Wang, Ph.D., SVP at Simcere Pharmaceutical Group; and Marian Nakada, Ph.D., VP of Venture Investment at JJDC, JNJ.

Key Insights on Collaboration with Big Pharma

The discussion began with the panel confirming that large pharmaceutical companies will continue to rely on small biotech firms for innovative assets to replenish their pipelines. John revealed that big pharma often targets up to 50% of late-stage assets from external sources. Marian emphasized that small biotech companies, leveraging their agility and focus, must ensure their innovations align with big pharma’s needs and produce high-quality data.

Strategies for Successful Collaborations and Deals

When discussing how to establish successful collaborations or business development deals with big pharma, Chong suggested that securing initial funding from a pharmaceutical company's venture branch can be an effective strategy. This often increases the likelihood of future collaboration. Marian noted that companies are generally acquired rather than sold, so creating assets that are crucial to sustaining a pharmaceutical company's franchise can be a significant advantage during negotiations. Additionally, leveraging competition to secure better terms can be beneficial. The panel agreed that small biotech firms should consider a "dual process" approach, seeking both funding and collaboration with big pharma simultaneously. For instance, Progeologix successfully used its Series B funding round as leverage during M&A discussions with JNJ, resulting in an $850 million cash deal. Erica, an experienced biopharma lawyer, highlighted that licensing agreements require both parties to work together to ensure the success of the "baby product." She frequently observes that collaborations fall apart not due to scientific issues, but due to misaligned objectives. Therefore, effective alliance management is crucial for achieving successful outcomes.

Funding Preferences in the Current Market

The panel also addressed funding preferences, such as IPOs and PIPEs. Chong stressed that, given the current macroeconomic challenges and backlog pressures on biotech IPOs, small biotech firms should prioritize raising funds by any means necessary and not overly concern themselves with dilution. "Life is much simpler with more money!" Erica reminded the audience that NASDAQ imposes stricter requirements, which raises the bar to prevent potential "pump and dump" activities.

Hot Therapeutic Areas 

Regarding the most promising therapeutic areas, the panel highlighted immunology & inflammation (I&I), metabolic diseases, radiopharma, in vivo Car-T, and Alzheimer's disease. Conversely, investors are wary of gene and cell therapies, although cell therapies have recently shown promise in autoimmune diseases. Marian also noted that immuno-oncology (IO) in oncology is losing its appeal due to the lack of reliable translational animal models, limited monotherapy efficacy, and unclear combination strategies.

Impact of the Inflation Reduction Act (IRA) 

The panel discussed the potential impact of the Inflation Reduction Act (IRA) on the biotech sector. Both investors noted that while the IRA has not yet significantly affected early-stage investment decisions, it might prompt strategic adjustments in the future. John emphasized the importance of selecting initial indications wisely, while Chong advised biotech firms to be strategic in development, such as designing two molecules for different indications. Erica highlighted the complexities the IRA introduces into commercially reasonable efforts (CRE) and royalties in collaboration agreements.

BioSecure Act and Its Implications

Finally, the panel explored the potential passage and impact of the BioSecure Act. All panelists believe it will pass, though they noted that companies will need time to adapt. The Act may lead to partial or full decoupling from Chinese CDMOs, but full decoupling is unlikely to happen quickly. Eric noted that the bill has evolved, with the latest version including a grandfather clause allowing companies until 2032 to phase out relationships with Chinese CDMOs. Compliance will become more complex,particularly in contractual negotiations.

John mentioned that while the Act might not immediately affect day-to-day operations, it has already caused hesitation among non-Chinese investors and companies. Marian added that many biotech companies dependent on WuXi and other Chinese CDMOs are now seeking alternatives, leading to the emergence of new companies to fill the gap. The industry is already adjusting its supply chains in anticipation of the potential new regulations, even before they take effect. 

Conference Agenda: 

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