AI-powered drug discovery: update (X)
✴️ Talem Therapeutics, ✳️ Xyphos Biosciences, 💠 Genesis Therapeutics, 🔷 Ribometrix, 🔶 Astrogen, ⚜️ Iktos, 🌀 Nuntius Therapeutics, 🔰 AIRNA and ✅ Generate Biomedicines
“Leadership is not domination, but the art of persuading people to work toward a common goal.”
Daniel Goleman, Emotional Intelligence
For the previous newsletters of this series of updates specifically on AI drug discovery companies with assets in preclinical and clinical trials 👉
Index for “AI-powered drug discovery: update part X” 🧵
Talem Therapeutics a subsidiary of IPA
Xyphos (an Axella company) in collaboration with IPA (utilizing LENSᵃⁱ from BioStrand, a subsidiary of IPA)
Talem Therapeutics LLC
Talem Therapeutics (2019, Canada) is a subsidiary of ImmunoPrecise Antibodies (IPA) and is focused on the discovery and development of next-generation human monoclonal therapeutic antibodies. By using the proprietary antibody discovery platforms and innovative technologies housed at IPA, Talem aims to accelerate novel, therapeutic antibody treatments to the clinic through strategic alliances and partners.
IPA (1983, Canada) (NASDAQ: IPA) is a progressive, scientific Contract Research Organization (CRO) recently ranked by one of the pharmaceutical industry’s most trusted independent market research sources with the highest competitive score for its antibody service portfolio. On September 26, 2024, IPA announced the clinical progress achieved with rabbit monoclonal antibodies designed and developed using IPA’s proprietary B Cell Select platform for the clinical-stage company, OncoResponse Inc. This achievement underscores IPA’s leadership as a Contract Research Organization creating high-quality therapeutic antibodies, while pioneering work in the field of rabbit monoclonal antibody development (ImmunoPrecise Antibodies Advances Therapeutic Innovation with Groundbreaking Rabbit Antibody Developments).
The B cell Select technology enables the interrogation of 10 million immune cells to generate native, monoclonal antibodies from immunized animals that specifically target an antigen and allow for the rapid selection of top candidates, increasing the success rate of an antibody discovery program. The platform also harnesses the power of the immune system to generate natural pairing of the antibodies produced by selected B cells (for more IPA: Antibody Discovery and Characterization).
Part of IPA is also BioStrand—founded in Belgium in 2019—an independently operating subsidiary of IPA at the intersection of biotherapeutics and AI. Biostrand has a patented LENSai™ Integrated Intelligence Technology powered by HYFTs® (Universal FingerprintsTM), that seamlessly integrates massive data from diverse data sources, to enhance LLMs and accelerate antibody discovery.
Talem Therapeutics and BioStrand (the two subsidiaries of IPA) have partnered to enhance Talem's lead therapeutic assets using BioStrand's LENSai software suite, which includes over 80 in silico applications. In particular, by analyzing diverse data sources LENSai can identify new antibody targets and predict binding affinities, as well as design and optimize antibody sequences and predict potential side effects, immunogenicity and therapeutic applications. To do so, HYFT (that is their proprietary transversal language) uncovers meaningful patterns, sequences, connections and insights from data, empowering scientists to make faster and more informed decisions. Moreover, HYFT can unify, organize and standardize all omics data, which enables scientists to collaborate and perform more efficient and accurate analyses.
Overall, LENSᵃⁱ seamlessly integrates:
Sequence (DNA-RNA-Protein),
Structure (AlphaFold, ESM-2, Rosetta Fold, Cryo-EM, Crystallography) and
Text (Peer-Reviewed Literature, Patents, Clinical Trials).
Following Talem’s and BioStrand’s partnership:
On March 15, 2023, IPA announced that Talem and Libera Bio S.L. (a private Spanish company, spun off from the University of Santiago de Compostela, Galicia, Spain), have signed a collaboration agreement to jointly address intracellular targets. It is estimated that 75% of disease-causing targets are located inside cells. Some of the most elusive cancer targets are expressed inside tumor cells. Because they are so difficult to address, they have sometimes been deemed “undruggable” and thus represent high unmet medical needs. For this reason, this partnership will leverage BioStrand’s LENSai® Full Suite of Integrated Intelligence Technology® and Libera Bio’s Multifunctional Polymeric Nanocapsules (MPN Technology®) (ImmunoPrecise Antibodies’ Subsidiary Talem Therapeutics Announces a Multi-Target AI-Driven Antibody Discovery Collaboration with Libera Bio) for the identification of undrugrable targets.
Moreover, on March 30, 2023 IPA announced a research collaboration and exclusive option license agreement with Xyphos Biosciences, Inc. (a wholly owned subsidiary of Astellas Pharma Inc, TYO: 4503). Under the terms of the agreement, the companies will jointly conduct research activities to identify and optimize proprietary LENSᵃⁱ in silico generated antibodies, targeting an undisclosed target in the tumor microenvironment (TME), as potential therapeutic development candidates. Targeting this molecule has the potential to markedly enhance anti-tumor immunity with other Astellas therapies including chimeric antigen receptor-based (CAR) technologies. Astellas will have the exclusive option to license any development candidates generated as part of the collaboration. (ImmunoPrecise’s Subsidiary Talem Enters into Exclusive Research Collaboration and License Option Agreement with Astellas)
In Tandem’s pipeline you can find the following assets:
🦚 TATX-20, CAXII, IO (Immuno-Oncology) ONC (Oncology)
CAXII is overexpressed in various cancers such as renal, breast, colon, cervical and ovarian. Importantly, inhibition of CAXII activity has been shown to reduce tumor size, inhibit tumor migration and to restore sensitivity to chemotherapy in preclinical models.
Talem has developed an antagonistic, fully human monoclonal antibody highly specific for CAXII, a lead candidate for the treatment of ovarian cancer.
🦩TATX-24, CD3, IO
Many solid tumors are poorly immunogenic as the binding of monoclonal antibodies to the tumor associated antigen (TAA) often fails to induce the required immune response for tumor cell killing. This renders immunotherapy less effective. Combining anti-TAA binding capability with anti-CD3 T cell engagement into one bispecific molecule enables the recruitment and activation of T cells to increase immunotherapy efficacy.
Talem has developed anti-CD3 Fabs specifically directed against CD3δε, which are expected to reduce cytokine release (a side effect of first generation of T cell engagers, leading to severe side effects and a narrow therapeutic window.). These Fabs are available to combine with anti-TAA arms of potential partners of the generation of novel T cell engaging bi-, tri- and multi- specific molecules.
🦆 TATX-25, Undisclosed, IO, ONC
Partner Pierre Fabre.
On October 07, 2021, IPA and the Pierre Fabre pharmaceutical group announced that Talem and Pierre Fabre have entered a multi-year, multi-target research collaboration with the goal to discover and develop therapeutics antibodies for up to nine targets. This strategic collaboration is expected to help expand Talem’s portfolio of novel antibodies across oncology (Talem Therapeutics Announces Multi-Target Antibody Discovery Research Collaboration with Pierre Fabre).
🦢 TATX-28, B7-H3, IO
Undisclosed partnership
🦤 TATX-112, TrkB, IO, ONC
Tropomyosin receptor kinase B (TrkB) is a receptor tyrosine kinase that is implicated in various solid tumors. Currently, therapeutic options for TrkB targeting are restricted to pan-Trk inhibitors, which lack specificity and cause side effects. The use of monoclonal antibodies specifically binding TrkB for the intracellular delivery of toxic payloads is anticipated to increase safety and efficacy of TrkB-directed cancer therapies.
In April 23, 2023, Talem presented a scientific poster, at the annual AACR meeting in Orlando, Florida, with their latest data on the development of bispecific T-cell engagers targeting TrkB. Tandem shared data demonstrating the evidence for the potential therapeutic ability to recruit and activate T cells to target TrkB-specific tumors, in what they believe may be a safer, more effective, and more targeted cancer therapy. The importance of the invention was appreciated in a provisional patent application filed by Talem Therapeutics to the United State Patent and Trademark Office. (ImmunoPrecise Presents Novel T-Cell Engaging Bispecific Antibodies Addressing a Unique Oncological Target, Tropomyosin Receptor Kinase B, Associated with Poor Prognosis and Survival Rates)
🦜TATX-200, TrkBx CD3, IO, ONC
The (over) expression of the Tropomyosin kinase B (TrkB) and (over) activation of the TrkB signaling pathway they both play an important role in various solid malignancies, including breast cancer (BC) and are associated with poor prognosis. Preclinical studies have demonstrated that targeting the TrkB pathway can reduce BC cell growth and metastasis, but current TrkB-directed treatment options are not specific. Additionally, BC are not highly immunogenic, rendering immunotherapy less effective.
By combining Talem’s proprietary anti-TrkB antibody arms with proprietary anti-CD3δε T cell engaging antibody arms in a bispecific format, a novel and effective immunotherapeutic molecule against BC is being developed with the aim of improving therapeutic options.
🕊️ TATX-03, SARS-CoV-2, ID
One of Talem’s most advanced development programs, TATX-03 (an anti-SARS-CoV-2 PolyTope), is a rationally designed, fully human, 4-antibody combinational therapy containing synergistic, potently neutralizing monoclonal antibodies against non-overlapping epitopes on SARS-CoV-2 spike trimer.
🐦 TATX-21, ALK1, OP (Ophthalmology)/VD (Vascular Disease)
Activin receptor-like kinase 1 (ALK1), a member of the TGF-β receptor superfamily, is preferentially expressed on endothelial cells. Its ligands are BMP9 and BMP10. Impaired BMP9/ALK1 signaling is associated with various vascular pathologies such as diabetic retinopathy, diabetic kidney problems and pulmonary arterial hypertension (PAH).
Talem is developing agonist antibodies specific for ALK1 with the aim to generate a safe and effective therapeutic for these vascular pathologies.
For more:
Jennifer Bath on IPA's AI-Driven Drug Discovery: Solving Data Overload in Pharmaceuticals - 56008944
Large Language Models Revolutionizing Drug Discovery: BioStrand
Xyphos Biosciences Inc
Xyphos Biosciences (an Astellas Pharma, Inc, TYO: 4503, company) located at South San Francisco, California (2004), is featuring the ACCELTM technology (Advanced Cellular Control through Engineered Ligands), a CAR (chimeric antigen receptor) technology platform for immune cell therapies. On December 26, 2019, Astellas and Xyphos announced that Astellas has acquired Xyphos. Considering the acquisition, $120M was paid upon closing of the acquisition and Xyphos became a wholly owned subsidiary of Astellas. In addition to this payment and potential future development milestone payments, it will provide a total transaction value of $665M.
As of March 30, 2023, Xyphos Biosciences has a research collaboration and exclusive option license agreement with IPA to jointly conduct research activities to identify and optimize proprietary LENSᵃⁱ in silico generated antibodies, targeting an undisclosed target in the tumor microenvironment, as potential therapeutic development candidates. Targeting these molecules has the potential to markedly enhance anti-tumor immunity with other Astellas therapies including chimeric antigen receptor-based (CAR) technologies. Astellas will have the exclusive option to license any development candidates generated as part of the collaboration.
Xyphos’ Immuno-Oncology pipeline (now part of Astellas) includes:
🎾 Oncolytic Virus (OV)
ASP1012 (systemic OV leptin IL-2 fusion) in phase 1 in collaboration with KaliVir Immunotherapeutics.
On October 24, 2023, KaliVir Immunotherapeutics Announces FDA Clearance of Investigational New Drug (IND) for Systemic Oncolytic Virus ASP1012 for Phase I Clinical Trials for Locally Advanced or Metastatic Solid Tumors.
Licensed to Astellas, ASP1012, reaches and destroys cancer cells and activates anti-cancer immunity through expression of therapeutic transgenes.
🏸 Bispecific Immune Cell Engager
ASP2138 (anti-claudin 18.2 and anti-CD3 bispecific antibody) in phase 1 in collaboration with Xencor.
Xencor, a clinical-stage biopharmaceutical company, through its XmAb protein engineering platform is developing a broad pipeline of drug candidates (engineered antibodies and cytokines) that are optimized to treat patients with cancer and autoimmune disorders.
On August 02, 2022, Caris Life Sciences and Xencor signed a target 🎯 discovery collaboration and license agreement for novel XmAb bispecific antibodies. Caris has a comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) platform and AI/ML applications.
ASP1002 (bispecific immune cell engager) in phase 1.
NOT DISCLOSED (probody T cell engagers) in preclinical in collaboration with CytomX.
On March 18, 2024, CytomX Therapeutics Announced Milestone Achievement in PROBODY® T-Cell Engaging Bispecific (TCB) Collaboration with Astellas. Initiation of GLP toxicology study for the first clinical candidate in the collaboration triggers a $5M milestone payment to CytomX.
🏏 Small Molecule
ASP1570 (DGKζ inhibitor) in phase 1
🏑 Cell Therapy
ASP2802 (CD20 convertible CAR-T) in phase 1
NOT DISCLOSED (UDC-NK) in discovery
NOT DISCLOSED (convertibleCAR-T) in discovery in collaboration with Poseida Therapeutics.
On May 14, 2024, it was announced a strategic research collaboration and license agreement between Poseida and Astellas' wholly owned subsidiary, Xyphos Biosciences, to develop novel cell therapies for solid tumors (convertibleCAR®). Under the research agreement, Poseida is receiving $50M upfront plus potential development and sales milestones and contingency payments of up to $550M in total and will be reimbursed for costs incurred as part of the research agreement. This new collaboration expands the strategic relationship between the companies, which began in 2023 with Astellas' $25M equity investment in Poseida and concurrent one-time $25M payment for a right of exclusive negotiation and first refusal to license Poseida's P-MUC1C-ALLO1 program also targeting solid tumors.
NOT DISCLOSED (in vivo convertibleCAR-T) in discovery in collaboration with Kelonia.
Genesis Therapeutics Inc
Genesis Therapeutics (South San Francisco, California, US, 2019) is accurately predicting ADMET by allowing researchers to use neural networks and biophysical simulation to generate and optimize molecules. Genesis is a privately-held company inventing and deploying state-of-the-art AI techniques to augment drug discovery and development. They are unlocking novel protein targets, exploring untapped chemical space and accelerating the development of critical new medicines with their AI platform (GEMS), that combines 3D structure-aware deep neural networks, new molecular simulation methods and a massively scalable molecular generation engine. GEMS, which integrates proprietary diffusion models, language models and physical ML simulations for molecular generation and property prediction, offers multi-task ADME, predictions for protein-ligand complexes and selectivity predictions via novel integration of ML + physics.
Genesis is working right now with the following AI-Enabled small molecule drug candidates:
🐞 Oncology: Using GEMS to generate and optimize first- or best-in-class small molecules for difficult biological targets, which offer potential to advance the treatment of difficult cancers.
Multiple lead candidates for highly potent and selective pan-mutant allosteric inhibitors of PIK3CA.
Genesis Therapeutics Inc. has disclosed phosphatidylinositol 3-kinase α (PI3Kα) (H1047R mutant) inhibitors reported to be useful for the treatment of cancer.
🐛 Immunology: Using GEMS to generate and optimize first-in-class small molecules for well-validated targets, as well as novel immunology targets.
Multiple targets for autoimmune disorder.
Moreover, Genesis has partnered so far with multiple industry leaders to amplify the impact of their AI platform for drug discovery:
In 2020, Genesis, a Stanford University spinout company, announced that it has entered into a multi-target collaboration agreement with Genentech to leverage Genesis’ graph ML and drug discovery expertise to identify innovative drug candidates.
In 2022, Genesis partnered with Lilly (NYSE: LLY) to deploy GEMS across a range of therapeutic areas. Genesis received $20M in upfront payment to collaborate on 3 initial targets, with a potential total deal value of $670M.
On September 10, 2024, Gilead inks $35M collaboration with AI drug discovery outfit Genesis. Gilead (NASDAQ: GILD) has agreed to pay its new partner $35M up front for AI-based drug discovery work on three undisclosed targets. Further, Gilead will have an option to nominate additional targets for a predetermined per-target fee.
Finally, on August 21, 2023 Genesis announced that it has closed an oversubscribed $200M round of Series B financing, to evolve into a clinical stage company, further invest in its state-of-the-art AI platform and expand its discovery pipeline (Genesis Therapeutics Closes Oversubscribed $200 Million Series B). This series B raise brings Genesis’ total capital raised since inception to over $280M.
For more about ADMET and AI Drug Discovery:
Ribometrix Inc
Ribometrix (2014, US) is leveraging proprietary RNA structure determination, state-of-the-art RNA tools and technologies and complementary AI/ML capabilities to directly target and modulate RNA biology. Ribometrix has risen to the challenge of addressing “undruggable” proteins by preventing the translation of their mRNAs, leading to a reduction of the target disease-causing protein. Their platform modulates RNA biology for therapeutic effect via independent yet related strategies to develop small molecule therapeutics: direct targeting of complex RNA structures, targeting of RNA/RNA-binding protein interactions and development of RNA degraders. Among their partners you can find Genentech and Vertex.
On January 6, 2021, Ribometrix announced a strategic collaboration with Genentech, a member of the Roche Group, to discover and develop novel RNA-targeted small molecule therapeutics against several targets. Ribometrix will apply its proprietary discovery platform to identify and optimize small molecule compounds that modulate RNA function by targeting three-dimensional (3D) RNA structures.
On September 30, 2019, Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) and RNA therapeutics developer Ribometrix announced that the companies have entered into a strategic collaboration to discover and develop novel RNA-targeted small molecule therapeutic candidates for serious diseases.
Right now at Ribometrix they are building a comprehensive internal pipeline of drug candidates that deliver on the promise of modulating RNA biology for therapeutic benefit:
🥁 elF4E Protein, Oncology: Lead Optimization
On April 07, 2024, Ribometrix shared the First c-MYC Data Validating RNA-Targeting Platform and Demonstrated Synergistic Potential of eIF4E Program at AACR 2024 for
Identifying a small molecules targeting c-MYC (a validated but historically undruggable cancer driver),
Demonstrating direct binding of small molecules to c-MYC RNA and reduction of associated protein levels (longtime goal of RNA therapeutic development) and
Demonstrating in vivo tumor regression in combination with in vitro data supported efficacy in drug-resistant tumors with the RNA-binding protein inhibitor program targeting eIF4E.
🪘 c-MYC, RNA, Oncology: Lead Optimization
On September 16, 2024, Ribometrix presented the latest in vitro and in vivo data from its eIF4E program regarding a small molecule eIF4E inhibitor, RBX-6610, as a potential treatment for KRASG12C mutant non-small cell lung cancer (NSCLC) patients, that acquire resistance with the two already approved therapies for KRASG12C mutant NSCLC. RBX-6610 is creating a significant opportunity for a therapy that re-sensitizes tumors to KRAS inhibition. Ribometrix’s data supports RBX-6610’s ability to deliver this mechanism in combination with the approved therapies.
🎻 Regnase-1, Protein, ImmunoOncology: Hit to Lead
🪕 Multiple Programs, RNA, Oncology: Target-to-HTS
🎸 Multiple Targets, RNA, Undisclosed
🎺 Multiple Targets, RNA, Undisclosed
Iambic Therapeutics (formerly known as Entos) and Lundbeck have just entered into a strategic research collaboration focused on the discovery of a small-molecule therapeutic for the treatment of migraine.
In the research partnership announced this week 📢 with Lundbeck, Iambic will use its AI drug discovery platform to accelerate research into neurological disease (migraine) – further expanding its potential impact in additional therapeutic areas.
Iambic is also developing an internal pipeline of candidates that includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs.
For more about Iambic’s pipeline:
Astrogen Co Ltd
Astrogen (S. Korea) is a clinical and research-oriented biotech company in South Korea focused on developing innovative new drugs for neurological diseases. Astrogen Co, Ltd was founded in 2017 by a pediatric neurologist (Su-Kyeong Hwang, MD) specializing in the development of small molecule based therapies. One of their flagship products in development is their lead candidate AST-001, under phase 3 clinical development in S.Korea for Autism Spectrum Disorder. AST-001 received approval from the Ministry of Food and Drug Safety on June 16, 2023.
On January 05, 2022, the AI drug discovery company Iktos and Astrogen announced that they have entered into a research collaboration agreement aimed at the discovery of innovative small molecule pre-clinical drug candidates for Parkinson's disease (Parkinson’s Drug Discovery Collaboration Between Astrogen, Iktos to Leverage AI Platform). Under the terms of the agreement, whose value was not disclosed, Iktos will apply its generative learning algorithms to identify new molecular structures with the potential to address a specific, undisclosed, marker of Parkinson’s disease (PD). Astrogen will provide in-vitro and in-vivo screening of lead compounds and pre-clinical compounds. While both companies will contribute to the identification of new small-molecule candidates, Astrgoen will lead the drug development process from the pre-clinical stages.
Astrogen, apart its lead candidate AST-001 under phase 3 clinical development for autism disorder, is currently working on the following programs:
✳️ AST-003 (ASD, autism disorder), AST-004 (Rett Syndrome), AST-031 (ADHD, attention deficit disorder), AST-035 (GMB, glioblastoma), AST-030 (PD/Parkinson’s disease, PF/Pulmonary Disorder), AST-038 (NF1, neurofybromatosis type 1) and AST-008 (Dravet syndrome) in preclinical phase. And
✳️ AST-029 (PD) in lead optimization.
Astrogen right now is pursuing an IPO (initial public offering) with the goal of listing on the KOSDAQ market within the year (2024), and plans to start construction of a factory that meets manufacturing and quality control standards (GMP) in Gijang, Busan in the second half of this year (아스트로젠 자폐스펙트럼 치료제, 개발단계 희귀의약품 지정).
Iktos SA
Iktos (2016, Paris, Ile-de-France, France) is specialized in the development of AI solutions applied to chemical research, more specifically medicinal chemistry and new drug design. Iktos is offering Makya, a generative AI-driven ligand and structure-based de novo design software for chemical space exploration and multi-parametric optimization (MPO) of lead compounds, available either as a SaaS platform or for implementation on customer premises or in the customer’s Virtual Private Cloud (VPC). Makya’s user-friendly interface enables it to be used by medicinal or computational chemists and can also be operated as a Python package through a Jupyter notebook interface. Iktos also released Spaya, an AI-based retrosynthesis platform and Spaya API, a high throughput synthetic accessibility scoring tool for virtual molecule libraries.
At Iktos, by leveraging cutting-edge AI and robotics to advance drug discovery projects rapidly, they delivered so far the following preclinical candidates in less than 2 years:
1️⃣ MTHFD2, Inflammation auto-immune diseases, Lead Optimization.
MTHFD2 is a mitochondrial enzyme playing a crucial role in controlling the fate and function of Th17 (characterized by production of IL-17) cells, and its inhibition promotes a Treg cell-like phenotype (Treg cells produce anti-inflammatory cytokines IL-10 and TGF-β, suppress activity of a variety of immune cells, and thereby inhibit immune responses). MTHFD2 deficiency has been shown to reduce disease severity in multiple in vivo inflammatory disease models.
By applying the AI-driven drug discovery platforms, Makya and Spaya, novel, potent and selective MTHFD2 inhibitors were identified like for example:
IKT525, a representative molecule from their lead series, a potent (IC50 < 5nM), selective (>1000X over MTHFD1), and potential first-in-class MTHFD2 inhibitor with desirable drug-like properties.
Preclinical candidate nomination is expected by 2025.
2️⃣ Confidential Target, Oncology, Hit-to-Lead.
3️⃣ Confidential Target, Oncology, Hit-to-Lead.
4️⃣ Confidential Target, Immuno oncology, Lead Optimization, A shared program.
On March 05, 2024 Elsevier and Iktos partnered to deliver an AI-driven synthetic chemistry platform for drug discovery. By combining the world’s largest chemistry database, Reaxys from Elsevier, with cutting-edge AI from Iktos, the new platform will enable pharmaceutical companies to identify pre-clinical drug candidates faster.
On July 08, 2024 Iktos acquired Synsight, a life sciences technology company specializing in protein-protein and RNA-protein interactions-targeted drug discovery. Synsight is a deep tech company developing a screening technology that enables the development of effective first-in-class drug candidates for RNA targeting, based on a discovery platform of AI and cell imaging. The French Synsight developed the Microtubule Bench technology (MT bench®), from a research tool to an industrialized cell testing to screen molecules by microscopy, making possible to identify and quantify the modulations of small molecules on proteins and nucleic acids with convergence of High-Content.
Moreover, Iktos has collaborations with: Merck KGaA, Darmstadt (ETR: MRK) (2020), Kadmon (a clinical-stage biopharmaceutical company based in USA, May 2021), UCB (EBR: UCB) (a global biopharma company focusing on neurology and immunology, May 2021), Astrogen (a clinical and research-oriented biotech company in S.Korea focused in developing innovative new drugs for neurological diseases, January 2022), Ono Pharmaceuticals Co from Japan, with a focus on oncology, immunology and neurology research (March 2022), Teijin Pharma based in Japan (April 2022), Sygnature Discovery (May 2022), Zealand Pharma A/S (OTCMKTS: ZLDPF) (a biotechnology company focused on the discovery and development of peptide-based medicines, June 2022), Galapagos (NASDAQ: GLPG) (formerly known as Galapagos Genomics is leading Belgian global biopharmaceutical company, June 2022), Kissei Pharmaceutical Co (TYO: 4547) (a Japanese pharmaceutical company specialized in the field of urology, kidney-dialysis and unmet medical needs, July 2023), Curreio (a Japanese company specializing in structural analysis of biomolecules using cryo-electron microscopy) and Bayer’s Crop Science (a Bayer division with its industry-leading R&D pipeline and portfolio of seeds & traits, crop protection and digital farming solutions, December 2023).
Finally, on March 9, 2023 Iktos announced the closing of a €15.5M Series A financing to expand its existing SaaS software and to launch Iktos Robotics: a unique drug discovery platform which combines AI and automation of chemical synthesis. The funding round was co-led by new investors M Ventures and Debiopharm Innovation Fund with participation from Omnes Capital (Iktos raises €15.5m Series A round to expand its artificial intelligence-based drug discovery technologies and solutions).
Nuntius Therapeutics Ltd
Nuntius Therapeutics (2021, UK, US) is dedicated to currently incurable rare diseases, delivering large genetic payloads into the correct cells, enabling physicians to treat their patients with efficient therapies. They use cell-specific nanocarriers to develop mRNA and gene editing therapies.
On June 05, 2024, Nuntius published its ML approach to discovering high-performing mRNA nanocarriers in the journal of Advanced Science (In Silico Screening Accelerates Nanocarrier Design for Efficient mRNA Delivery). In particular, Nuntius’ high-throughput, in silico screening of delivery vehicle candidates significantly reduces the time and cost required to bring mRNA therapies to the clinic.
Computational models capable of predicting clinically relevant physio-chemical properties of dendrimer-lipid nanocarriers, along with their mRNA payload delivery efficiency in human cells are developed and then deployed on a large theoretical nanocarrier pool consisting of over 4.5 million formulations. Top predictions are synthesized for validation using cell-based assays, leading to the discovery of a high quality, high performing candidates. These methods enable rapid, high-throughput, in silico pre-screening for high-quality candidates, and have great potential to reduce the cost and time required to bring mRNA therapies to the clinic.
On August 15, 2024, Nuntius announced that they have entered into a collaboration agreement with Taiho Pharmaceutical Co., Ltd, a leading company in Japan for developing innovative medicines for the treatment of cancer. Taiho will use Nuntius’ cell-specific peptide dendrimer- and lipid-based nanocarriers to develop novel mRNA cancer immunotherapies. This collaboration follows a successful feasibility study that demonstrated the capabilities of Nuntius’ cell-specific peptide dendrimer- and lipid-based nanocarriers. Nuntius focuses on creating new mRNA therapeutics by combining patented delivery technology, ML and advanced nucleic acid engineering (Nuntius partners with Taiho to develop mRNA cancer therapies).
Taiho Pharmaceutical Co., Ltd. (大鵬薬品工業株式会社) is a Japanese pharmaceutical company, and a subsidiary of Otsuka Holdings (TYO: 4578), which focuses on developing cancer treatments. Taiho, headquartered in Tokyo, Japan, is an R&D-driven specialty pharma focusing on the three fields of oncology, allergies and immunology and urology.
siRNA-loaded lipid nanoparticles (LNPs) for gene therapy
In a study published in the Journal of Controlled Release just this week (by a group of researchers at the Chiba University, Japan) it was revealed how different mixing methods impact the effectiveness of siRNA-loaded lipid nanoparticles (LNPs) for gene therapy (NMR-based analysis of impact of siRNA mixing conditions on internal structure of siRNA-loaded LNP).
This study aimed to assess the applicability of solution-state 1H NMR for molecular-level characterization of siRNA-loaded lipid nanoparticles (LNP).
siRNA therapies show promise for treating diseases like cancer and genetic disorders, but their effectiveness depends on proper delivery. This recent study found that the method of mixing siRNA with LNPs is key to success. Using NMR and small-angle X-ray scattering (SAXS), researchers revealed that different preparation methods affect the internal structure and siRNA distribution in LNPs, impacting their therapeutic potential. Optimizing these methods can enhance the efficacy of siRNA-loaded LNPs.
AIRNA Inc
AIRNA is a biotech company pioneering RNA editing therapeutics to restore the health of patients with rare and common diseases. AIRNA’s experienced team is aiming to advance a pipeline of RNA editing therapeutics driven by its powerful and flexible RNA editing platform, RESTORE+, designed to restore a patient’s health by creating genetic medicines for rare and common diseases.
RESTORE+ optimizes oligonucleotide sequences, chemistry and delivery for precise, efficient and safe RNA editing. AIRNA’s first product candidate is a potential best-in-class treatment for alpha-1 antitrypsin deficiency (AATD), a genetic condition implicated in severe lung and liver disease.
In 2023 the company emerged from stealth with a $30M initial financing led by ARCH Venture Partners. On July 31, 2024, AIRNA announced the successful closing of an oversubscribed $60M financing round, which brings the total Series A funding to $90M, to advance AIRNA’s lead product candidate into clinical trials and further develop AIRNA’s broad pipeline.
Generate Biomedicine Inc
Generate Biomedicines (2018, US), which is a Flagship Pioneering Company, exists at the intersection of ML, biological engineering and medicine and is using ML algorithms to generate novel sequences for proteins (antibodies, peptides, enzymes, stealth proteins) that have never been seen in nature. Generate Biomedicines released in 2012 its diffusion model for protein design called Chroma, that learns patterns in the 3D structures and amino acid sequences of proteins and protein complexes from the Protein Data Bank, and can then synthesize new protein molecules that adhere to specific principles while combining them in novel ways. Chroma is able to generate extremely large proteins and protein complexes (e.g. 30,000+ heavy atoms across 4,000+ residues) in a few minutes on a single commodity GPU.
In their pipeline you can find the following assets:
🐲 Immunology
🏵️ GB-0895, Severe Asthma, TSLP
By leveraging a proprietary a ML platform they identified a monoclonal antibody PRO-17101 that exceeded the affinity target, binding human TSLP with an affinity of 106 fM, a 20-fold improvement over the benchmark. Mutations were introduced into the Fc region of PRO-17101 to extend half-life to create GB-0895. PRO-17101 and/or GB-0895 were active in multiple cell-based TSLP stimulation assays with potencies generally exceeding the benchmark. In mouse models of allergic airway inflammation, PRO-17101 neutralized TSLP and reduced leukocytes, eosinophils and IgE in the bronchoalveolar lavage along with serum IgE and Th2 mediators. Binding of GB-0895 was specific for TSLP in a screen against over 6000 extracellular human proteins. In a cynomolgus monkey study, GB-0895 was well tolerated and displayed a pharmacokinetic profile predicted to fulfill the targeted dosing regimen.
GB-0895 has the potential for best-in-class dosing for patients with severe asthma.
A phase 1 dose escalation trial in asthma patients is underway and they successfully dosed the first patient in a study of GB-0895 in the United Kingdom (2024). The primary endpoint of the study, which will also be conducted in Germany, aims to evaluate the safety and tolerability of GB-0895 for subcutaneous administration, with the goal of selecting 1–2 doses/regimens to advance in development.
🏵️ GB-7624, Atopic Dermatitis, IL-13
Scaling the platform in immunology with a highly potent anti-IL-13 monoclonal antibody for certain type‑2 inflammation-mediated diseases, such as atopic dermatitis and an anti-hemagglutinin (HA) monoclonal antibody targeting influenza.
🏵️ mAb, Ulcerative Colitis, TL1A
🏵️ mAb, Atopic Dermatitis, OX40L
🏵️ Mono and combo incl. bs Ab Various Various
🦎 Immuno-oncology
🔆 Bispecific, NSCLC, Undisclosed (The University of Texas
MD Anderson Cancer Center)🔆 Armored CAR-T, Advanced Solid Tumors, Undisclosed (Roswell Park)
🐉 ADCs
🟧 Protein Binder, ADC Toxin Neutralizer, Free MMAE
🟧 ADC, Advanced Solid Tumors, Undisclosed
🦖 Infectious Disease
🟠 GB-0669, Covid-19 PrEP, SARS-CoV-2 S2
Continuing to progress the phase 1 study for GB-0669 (2024), a monoclonal antibody targeting the S2 stem helix, a highly conserved region of spike protein in SARS-CoV‑2. Safety has been shown for the first four of five planned cohorts, including the putative recommended dose; analysis of key biomarkers is ongoing. GB-0669 continues to show potent in vitro neutralization of all major variants tested to date.
🟠 mAb, Covid-19 PrEP, SARS-CoV-2 RBD cl.IV
🦕 Undisclosed, Amgen
🐊 Undisclosed, Novartis
On September 24, 2024, Generate announced a multi-target collaboration with Novartis (NYSE: NVS) to discover and develop protein therapeutics across multiple disease areas. The collaboration leverages Generate’s proprietary generative AI platform, “The Generate Platform,” to create potentially first- and best-in-class molecules through AI-based optimization and de novo generation.
Finally, on January 4, 2024 Generate announced an expansion of its collaboration agreement with Amgen (NASDAQ: AMGN).
Amgen has exercised its rights under the collaboration agreement to opt in for a sixth program. This represents the first expansion of the original agreement, and as a result, Amgen will make an undisclosed upfront payment and will pay up to $370M in future milestones and royalties up to low double digits for this new program.