RadioMedix, Inc.

As biopharma begins to scratch the surface of what AI-enabled protein design is capable of, Aizen Therapeutics is targeting the flipside of the coin. The San Diego-based startup, which emerged from stealth Thursday with $13 million in seed funding, aims to generate peptides that are the mirror image of naturally occurring molecules, and have the added bonus of improved stability and lower immunogenicity. Aizen's AI-powered DaX platform allows it to design D-amino acids, which are the exact opposite of nature's L-amino acids. The technology was spun out of the lab of California Institute of Technology professor David Van Valen, who is also the newco's scientific founder.With Thursday's financing, which is expected to provide more than two years of runway, Aizen is aiming to select an IND-enabling lead programme and secure a strategic partner that validates its mirror peptide technology. The company's backers include venture capital firms Wilson Hill, Madrona and Cercano.AI accelerationThe drug development space has been interested in D-amino acids for at least 20 years, Aizen CEO Ajay Kshatriya told FirstWord, given their therapeutically beneficial properties. When proteins composed of L-peptides are introduced to the body, they're quickly broken down, and the smaller pieces of amino acids are then clocked as foreign, triggering an immune response, he explained. However, proteases can't engage with mirror peptides, thus bypassing the breakdown process and avoiding alerting the immune system altogether. Several drugs that feature D-amino acids in their molecular makeup have been approved by the FDA, but designing entire mirror peptides has historically posed a time-consuming problem due to a lack of data. The entire process, if relying solely on wet lab work and a method called reverse mirror image phage display, could take one to three years, Kshatriya said. While Van Valen believed that the process could be sped up with generative AI (genAI), the next roadblock he faced was that the protein repositories assembled thus far relied completely on L-amino acids."AI needs data, and all the data in the Protein Data Bank, all the crystal structures and all the images, were all looking at L-proteins binding to L-receptors," Kshatriya said, adding that existing computational programmes such as AlphaFold and Rosetta were designed to work only for L-amino acids. "It's a pretty challenging transformation to leverage L-data and then design a D-model," he remarked. But, thanks to a "clever algorithmic design" and recent innovations in guided diffusion models, Van Valen was able to build and train a genAI programme to design D-peptides from scratch. More importantly, the Aizen team has shown that the algorithm works. The company's scientists synthesised D-peptides spit out by the model and then tested them against known receptors — and were able to demonstrate binding activity. With the scientific and technological groundwork laid for Aizen, the company has now begun to explore all the clinical applications of a compound that can now be designed in weeks, instead of years.  Best of both therapeutic worldsAccording to Kshatriya, the startup's mirror peptides are "ideal targeting vehicles" because they have the "benefits of size and tissue penetration of a small molecule, but the specificity of binding of an antibody."One application Aizen is pursuing is the development of peptides that target receptors at the interface of the blood-brain barrier, thus acting as a delivery vehicle to transport a linked payload into the brain. Another area ripe for innovation is radioligand therapeutics (RLTs), a modality that has seen big-ticket investments and deals from pharma this year (see – ViewPoints: Exploring the strategy behind Sanofi's recent investment in RLTs with global head of oncology Olivier Nataf and ViewPoints: RadioMedix CEO sees lead as the future of RLTs).Mirror peptides could grant cancer cell surface-specific targeting to RLTs, while also being able to penetrate deep into the tumour microenvironment, Kshatriya explained.Beyond those two applications, Aizen's DaX platform is capable of designing peptides for a variety of receptor classes, including GPCRs, transmembrane proteins and ion channels."We're in the early innings of the potential for computation and AI to impact the design of proteins," Kshatriya commented.

A month after making a foray into the bustling radioligand field, Sanofi is further allying itself with Orano Med, paying €300 million for a 16% stake in the alpha-focused radiopharma company. Last month, Sanofi teamed up with Orano Med and its partner RadioMedix, paying €100 million (about $110 million) in upfront payments to gain access to the duo’s experimental radioligand treatment, called AlphaMedix. They could also get up to approximately €220 million ($242 million) in aggregate sales milestones, plus tiered royalties. Sanofi plans to drive commercialization, while Orano Med steers manufacturing. “We are excited to partner with Orano in establishing a French leader that unites our respective expertise in biopharma and nuclear technology to drive groundbreaking progress in the fight against cancer,” Sanofi CEO Paul Hudson said Thursday in a statement when it disclosed the deal. Sanofi said in September the companies were finishing up a Phase 2 of AlphaMedix in certain neuroendocrine tumors (think Novartis’ Lutathera), and the data were “being discussed with the FDA for potential regulatory filing and approval.” AlphaMedix is a lead-212-based agent, which is part of the alpha class of radioligand therapies. Other companies in the lead-212, or ²¹²Pb, space include Perspective Therapeutics and Artbio . The companies now plan to work together to “further accelerate” Orano Med’s pipeline of next-generation radioligand medicines, according to the announcement. The investment arrives as Sanofi is rethinking its identity under Hudson’s leadership. The drugmaker is doubling down on immunology, trying to offload its consumer health unit Opella (though that is running into challenges in France ) and reshaping its oncology pipeline . Sanofi is a relatively late entrant to the radiopharma field compared to some of its pharma peers. The market has exploded in recent years with Bristol Myers Squibb , AstraZeneca , Eli Lilly and Novartis all buying radiopharma companies. Investors are also pouring cash into megarounds, with Bayer’s radioisotope supplier PanTera banking a $103 million round and multiple pharmaceutical makers backing Aktis Oncology’s $175 million Series B last month. Sanofi highlighted Orano Med’s “vast stock of raw materials and patented manufacturing process.” Orano Med has an alpha therapy production site near Indianapolis and started construction last year on a facility in France for the European market. The Orano Group subsidiary has a research unit in Plano, TX. Orano Med’s pipeline also includes prostate cancer and other solid tumor programs. It also has partnerships with Roche and Molecular Partners.

Sanofi is deepening its commitment to targeted radiation therapies for cancer with a €300 million equity investment in a new entity pursuing next-generation radioligand therapies. The new entity will operate under the brand of Orano Med, a subsidiary of Orano Group. Sanofi already has a relationship with Orano Med. Last month, the Paris-based pharmaceutical giant licensed rights to Alphamedix, a clinical-stage radiopharmaceutical that partners Orano Med and RadioMedix developed for neuroendocrine tumors. The €300 million (about $324.8 million) investment announced Thursday represents an equity stake of about 16% in the new entity, which is valued at €1.9 billion (about $2 billion). Sanofi said the entity will focus on the discovery, design and clinical development of next-generation radioligand therapies. Such therapies are comprised of a radioisotope attached to a targeting molecule that delivers the treatment to a specific cancer target. The goal of such therapies is to target the damaging radiation on cancer cells, limiting the impact to healthy cells. Sanofi said the therapies developed by the new Orano Med entity will employ various targeting agents to deliver lead-212, or 212Pb. sponsored content Upcoming Webinar: Battle of the Budget: Employers vs. Rising Healthcare Costs Gain valuable knowledge and practical insights on how employers are addressing an increasingly complex healthcare budget landscape. By Personify Health Orano Group, which is based in Paris and maintains U.S. headquarters in Bethesda, Maryland, provides products and services to the nuclear industry. This work generated €4.8 billion (about $5.2 billion) in revenue in 2023, according to the company’s annual report. The bulk of the revenue was from back end operations that include recycling used fuel, making storage containers for nuclear materials and transporting these materials, and dismantling nuclear equipment and facilities, the report shows. Orano Med is the nuclear medicine-focused subsidiary of the company focused on developing therapies based on 212Pb, a rare alpha-emitting radioactive isotope. The company says it has developed a unique process to extract and purify 212Pb from the recycling of drums used in mining activities. In addition to building plants in the U.S. and Europe that produce 212Pb for the clinical development and potential commercialization of targeted radiation therapies, Orano Med develops nuclear medicines under partnerships. R&D partners include Roche, Molecular Partners, and Crescendo Biologics. AlphaMedix, the therapy that is Orano Med’s most advanced program, was developed under a partnership with Houston-based RadioMedix. This therapy seeks out somatostatin receptors, a target highly expressed on neuroendocrine tumors. Chemotherapy is the standard treatment for this group of rare cancers primarily affecting the gastrointestinal tract. Under the partnership with RadioMedix, AlphaMedix has reached Phase 2 testing, but the results so far are being discussed with the FDA for a potential regulatory submission. In September, Sanofi announced a €100 million (about $110 million) deal to license AlphaMedix. The pharma giant could pay out up to €220 million (about $242 million) more if this radiopharmaceutical achieves milestones. presented by Health IT Accelerating Claim Processing: Strategies to Shorten the Life of a Claim These strategies and practices can significantly shorten the life cycle of claims, leading to quicker resolutions and improved financial outcomes. By Greenway Health Specific targets of interest for the new Orano Med entity were not disclosed. But Sanofi said efforts will focus on difficult-to-treat cancers, both hematological malignancies and solid tumors that have critical unmet medical need, including rare cancers such as multiple myeloma, acute myeloid leukemia, and certain types of lymphomas. The scope of the research will also include gastrointestinal and lung cancers. “We see opportunity in the innovative lead-212-based technologies being developed by Orano Med, which align with our commitment to advancing transformative therapies for unmet medical needs,” Houman Ashrafian, executive vice president, head of research and development, Sanofi, said in a prepared statement. Photo by Flickr user John Jones via a Creative Commons license