Bits In Bio Weekly - December 31st 2024
Updates From and Around the Bits in Bio Community
📢 Highlights
Fine-Tuned OpenFold Achieves 60X Better Peptide Design with Limited Data
Spatial Proteomics Claims Top Spot as Nature Methods' 2024 Breakthrough
Oncology to Immunology: Inside the Ikena-Inmagene Strategic Merger
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Low-N OpenFold fine-tuning improves peptide design without additional structures
High-affinity peptide binders are vital for therapeutic design, and machine learning-based in silico screening enhances their discovery. While structure-based prediction models like AlphaFold-Multimer demonstrate potential, their zero-shot performance remains limited for diverse peptide screening. Researchers from Dyno Therapeutics developed a fine-tuning framework for OpenFold, achieving 13-60x improvements in peptide design hit rates using minimal data. Fine-tuning on peptide-domain interactions not only enhanced binding predictions but also improved structural accuracy for peptide-protein complexes without additional training. The model surpassed base OpenFold and baselines like CNN and ESM2, excelling in shared and novel domain tasks. Notably, the shared domain task saw up to 60x enrichment of high-affinity binders, streamlining peptide screening. A new binding prediction head further increased accuracy for challenging domains, highlighting the potential of fine-tuning in peptide design and integration with generative tools like RFDiffusion.
Nature Methods Recognizes Spatial Proteomics as ‘Method of the Year’
Spatial proteomics, the study of the spatial distribution and function of proteins in cells and tissuesI, has been named "Method of the Year 2024" by Nature Methods for its ability to map protein localization and interactions with unprecedented resolution, revealing the organization of complex tissues. Key applications of this technology include the study of tumor microenvironments, immune cell infiltration patterns, and neuronal signaling pathways. Recent innovations have driven its adoption in oncology, where it provides unprecedented insights into heterogeneity within solid tumors and informs the development of precision therapies. The editors at a nature gave this explanation for their decision: "...we were excited by the recent development of DVP and other methods seeking new ways to explore the spatial proteome in greater depth and breadth. In addition, we were inspired by the current efforts of large consortia such as the Human BioMolecular Atlas Program (HuBMAP) and the Human Tumor Atlas Network (HTAN) not only to create large atlases of data for the scientific and medical communities, but also to develop tools to process, analyze, visualize and mine the data to go beyond the pretty pictures and deeper into biological discovery".
Behind the Deal: Ikena and Inmagene Merge to Target the Growing Atopic Dermatitis Market
The merger between Ikena Oncology and Inmagene Biopharmaceuticals marks a strategic pivot, creating InmageneBio focusing on IMG-007, an OX40-targeting monoclonal antibody. This news is particularly compelling as it highlights a rare shift in strategy: a struggling oncology company aligning with a privately held immunology leader to create a streamlined entity targeting a high-growth market. Backed by a $75 million private placement from top-tier investors, this merger offers exposure to a promising asset in IMG-007, which recently completed a phase 2a trial for atopic dermatitis. The drug’s longer half-life and non-T cell-depleting profile offer potential safety and dosing advantages over competitors like Amgen’s phase 3 candidate rocatinlimab and Sanofi’s amlitelimab. The atopic dermatitis market, valued at over $12 billion globally, continues to expand, driven by growing prevalence and demand for safer, more effective therapies. This shift also represents a value reset for Ikena, which struggled following setbacks in oncology. The newly formed InmageneBio targets a high-growth market segment by refocusing on immunology and inflammatory diseases, aligning with investor interest in assets with lower development risk and high commercial potential. With phase 2b trials for IMG-007 expected in 2025, the company is well-capitalized to generate significant returns for long-term stakeholders.
Tumor-Selective Immunomodulator Pioneer Akamis Bio Secures $60M Series A
Akamis Bio has successfully closed $60 million in Series A funding, alongside an unnamed new strategic partnership, to advance its tumor-selective immunomodulators (TSIMs). These proprietary cytokine-based therapies are engineered to selectively activate immune pathways within the tumor microenvironment, sparing healthy tissues and minimizing systemic toxicities. TSIM technology addresses limitations in systemic cytokine therapies, such as off-target effects, which have historically hampered clinical adoption. The funding will advance Akamis's primary candidate, NG-350A through a Phase 1b clinical proof-of-concept study, titled FORTRESS (NCT06459869) in patients with locally advanced rectal cancer. An intravenously delivered, transgene-armed tumor gene therapy designed to drive intratumoral expression of a CD40 agonist monoclonal antibody in metastatic epithelial-derived solid tumors.
Bristol Myers Squibb Validates Insitro's AI Approach to ALS With $25M Milestone Payment
One of the last standing from the first wave Bio Ai startups, Insitro, leveraging high-throughput data generation and machine learning, received a $25 million milestone payment from Bristol Myers Squibb for a successful Amyotrophic Lateral Sclerosis (ALS) target discovery campaign. The collaboration applies Insitro’s predictive models and AI platform tools to identify novel synaptic and neuronal targets linked to ALS. This achievement provides credibility for the potential of AI to de-risk therapeutic development, particularly in complex neurodegenerative diseases like ALS, where limited target validation across the industry has slowed drug approvals.
New Alnylam and Roche Partnership to Advance RNAi Treatment for Alzheimer's
Biotech giant Roche has deepened its collaboration with the Cambridge-based publicly traded biotech, Alnylam Pharmaceuticals, to co-develop and commercialize ALN-APP, an investigational RNAi therapeutic targeting amyloid precursor protein (APP) for Alzheimer’s disease. ALN-APP employs RNA interference (RNAi) to selectively silence APP production, addressing plaque formation, a central pathological feature in Alzheimer’s. The partnership builds on Alnylam’s platform successes, including FDA-approved RNAi therapies for rare genetic diseases like ONPATTRO and GIVLAARI, RNAi’s CNS applications represent a frontier in drug discovery for neurodegenerative conditions as drug makers try to develop countermeasures against the nightmare illness.
Syncromune Raises $100M to Advance Localized Cancer Immunotherapy
Florida-based Syncromune has raised $100 million to expand its platform, which integrates intratumoral delivery of oncolytic viruses with immunomodulatory agents. The biotech, which was founded in 2020 and is working on combination immunotherapies, expects to use the new funding on a Phase 2a for its drug candidate SV-102 for metastatic castration-resistant prostate cancer, also known as mCRPC. Oncolytic viruses selectively replicate within tumor cells, amplifying immune activation while sparing healthy tissue. Syncromune’s technology shows potential in addressing “cold” tumors resistant to immune activation. This funding supports preclinical studies and clinical trials targeting solid tumors. Localized immune activation is gaining attention as a method to reduce adverse effects seen with systemic immunotherapies.
$34M Investment Propels GemmaBio's Muscular Dystrophy Gene Therapy
One of two new companies spun out of the now-folded Gene Therapy Program at the University of Pennsylvania, GemmaBio has raised $34 million to advance its gene therapy programs targeting rare genetic diseases such as Muscular Dystrophy. Its focus on improving delivery vector specificity and reducing immunogenicity tackles longstanding challenges in the gene therapy modality. The company’s lead program addresses Duchenne muscular dystrophy using optimized capsids for efficient transgene expression. GemmaBio states that the funding will enable its IND-enabling studies and early clinical trials, and reflects a growing confidence in scalable gene therapies - once thought to be tantamount to science fiction - which are globally projected to reach $12 billion by 2028.
Repurposed Drug, Auvelity, Shows Promise for Alzheimer's Symptomology Mitigation
Axsome Therapeutics reported strong data for Auvelity, a combination of a MAOI bupropion and the over the counter cough drug dextromethorphan, for treating agitation in Alzheimer’s. Its dual-action mechanism on NMDA and monoamine systems addresses excitotoxicity and behavioral dysregulation, which otherwise give rise to a state where patients are unable to relax or stay still in any meaningful sense. Alzheimer’s-related agitation affects nearly half of patients and is linked to higher rates of institutionalization. Though its approach is curious to say the least, Auvelity could become the first approved therapy for this challenging condition.
AI Startup SandboxAQ Raises $300M for New Biopharma Applications
The 3 year old Palo Alto based tech company, SandboxAQ, has secured $300 million in funding to expand its “quantum-inspired” AI platform into biopharma applications. Its algorithms optimize protein-ligand interactions through sophisticated and quantitative molecular simulations, critical for early drug discovery. Partnerships with major biopharma companies highlight the impact of integrating AI in lead optimization processes.
New $190M Fund for Early Biotech and Medtech Launched by Xgan Venture Partners
Based in Milan, Italy - a city known more for fashion and culture than high technology - Xgen Venture Partners has garnered international attention after announcing that it has raised $190 million biotech fund to support early-stage innovations in RNA therapeutics, gene editing, and next-gen diagnostics. These high-risk, high-reward investments are critical for translating breakthrough technologies into clinical applications, say sources close to the company. The fund focuses on bridging preclinical innovations to clinical trials, addressing translational gaps that hinder early-stage biotech startups.
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