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.

Sanofi and Orano join forces to develop next-generation radioligand medicines PARIS, France I October 17, 2024 I Sanofi and Orano Med, a subsidiary of the Orano Group and a pioneer in the development of targeted alphatherapies in oncology, have entered into an agreement to combine their expertise in the fight against rare cancers and further accelerate the development of next-generation radioligand medicines. Building on the expertise and radioligand pipeline of Orano Med, Sanofi and Orano will invest in a new entity, operating under the Orano Med brand, and focusing on the discovery, design, and clinical development of next-generation radioligand therapies (RLTs) based on lead-212 ( 212 Pb) alpha-emitting isotopes. This agreement follows Sanofi’s announcement of an exclusive licensing agreement with Orano Med and RadioMedix to advance radioligand therapies (RLTs) in rare cancers with a focus on one late-stage project, AlphaMedix™. Targeted alpha therapy relies on a simple concept: combining the ability of biological vectors to target cancer cells with the short-range and highly energetic cell-killing capabilities of alpha-emitting radioisotopes. The vector directs the radioisotope to the target cancer cells expressing the specific marker, even when they have spread throughout the body. This unique mechanism of action aims to damage or destroy target cancer cells, while limiting impact on nearby healthy cells. This novel precision medicine approach aims at changing the standard of care in some rare cancers to extend patients’ lives and improve their quality of life. Paul Hudson CEO, Sanofi “We are excited to partner with Orano in establishing a French pioneer that unites our respective expertise in biopharma and nuclear technology to drive groundbreaking progress in the fight against cancer. As a French biopharmaceutical company, we are deeply committed to fostering and enabling innovation in our home country. This collaboration is part of a broader effort to strengthen our ties within the scientific community, both in France and globally, with the goal of advancing the development of cutting-edge treatments for patients.” Nicolas Maes CEO, Orano Group “The success of Orano Med is an example of our group’s ability to diversify beyond our core nuclear business. By applying our expertise in nuclear materials to fields like targeted alpha therapies, we are demonstrating that nuclear technology can have a positive societal impact, not just for energy and climate, but also for human health. This innovation reflects Orano’s commitment to exploring new opportunities and taking bold steps to address some of the world’s most pressing challenges.” Sanofi’s investment will further strengthen Orano Med and allow the company to accelerate the development of its pipeline, leveraging its unique capabilities in the discovery and development of lead-212 based therapies. Orano Med has also developed a highly differentiating global industrial platform, which, thanks to its vast stock of raw materials and patented manufacturing process, will ensure an independent, reliable, and scalable supply of lead-212 based therapies to patients worldwide. Houman Ashrafian Executive Vice President, Head of Research and Development, Sanofi “We are thrilled to invest in the promising field of radioligand therapies, a modality that holds potential for patients suffering from rare 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.” Julien Dodet President of the Governing Board, Orano Med “Sanofi’s partnership with Orano Med is a strong recognition of the potential of lead-212 based radioligand therapies to advance the treatment of cancers. This validates our strategy, having developed this expertise over the past 15 years, and reinforces our position as a leader in targeted alpha therapies. We look forward to combining Sanofi’s expertise with our R&D and world-class radiopharmaceutical capabilities to advance the development of potentially transformative therapies like AlphaMedix and make them available to patients in need as quickly as possible.” In striving to become a leading immunoscience company globally, Sanofi remains committed to advancing oncology innovation. The pipeline is being reshaped and prioritized, leveraging expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including rare cancers such as multiple myeloma, acute myeloid leukemia, and certain types of lymphomas, as well as gastrointestinal and lung cancers. Sanofi and Orano Med are members of the Paris Saclay Cancer Cluster and look forward to contributing to the ambitious agenda of the France 2030 plan to accelerate innovation in oncology. This agreement is subject to standard regulatory approvals required for transactions of this nature. Financial considerations Under the terms of the agreement, Sanofi will make an equity investment of €300 million, approximately 16% equity stake in the new entity valued at €1.9bn. About Sanofi We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY About Orano Med Orano Med, a subsidiary of the Orano Group, is a clinical-stage biotechnology company that develops a new generation of targeted therapies against cancer using the unique properties of lead-212 ( 212 Pb), an alpha-emitting radioisotope and one of the more potent therapeutic payloads against cancer cells known as Targeted Alpha-Emitter Therapy (TAT). The company is developing several treatments using 212 Pb combined with various targeting agents. Orano Med has 212 Pb manufacturing facilities, laboratories, and R&D centers in France and in the US and is currently investing to further expand its GMP-manufacturing capacities for 212 Pb radiolabeled pharmaceuticals in North America and Europe. As a recognized international operator in the field of nuclear materials, Orano Group delivers solutions to address present and future global energy and health challenges. Its expertise and mastery of cutting-edge technologies enable Orano to offer its customers high value-added products and services throughout the entire fuel cycle. Every day, the Orano group’s 17,500 employees draw on their skills, unwavering dedication to safety and constant quest for innovation, with the commitment to develop know-how in the transformation and control of nuclear materials, for the climate and for a healthy and resource-efficient world, now and tomorrow. SOURCE: Sanofi

Sanofi and Orano join forces to develop next-generation radioligand medicines Paris, October 17, 2024. Sanofi and Orano Med, a subsidiary of the Orano Group and a pioneer in the development of targeted alphatherapies in oncology, have entered into an agreement to combine their expertise in the fight against rare cancers and further accelerate the development of next-generation radioligand medicines. Building on the expertise and radioligand pipeline of Orano Med, Sanofi and Orano will invest in a new entity, operating under the Orano Med brand, and focusing on the discovery, design, and clinical development of next-generation radioligand therapies (RLTs) based on lead-212 (212Pb) alpha-emitting isotopes. This agreement follows Sanofi’s announcement of an exclusive licensing agreement with Orano Med and RadioMedix to advance radioligand therapies (RLTs) in rare cancers with a focus on one late-stage project, AlphaMedix™. Targeted alpha therapy relies on a simple concept: combining the ability of biological vectors to target cancer cells with the short-range and highly energetic cell-killing capabilities of alpha-emitting radioisotopes. The vector directs the radioisotope to the target cancer cells expressing the specific marker, even when they have spread throughout the body. This unique mechanism of action aims to damage or destroy target cancer cells, while limiting impact on nearby healthy cells. This novel precision medicine approach aims at changing the standard of care in some rare cancers to extend patients’ lives and improve their quality of life. Paul HudsonCEO, Sanofi“We are excited to partner with Orano in establishing a French pioneer that unites our respective expertise in biopharma and nuclear technology to drive groundbreaking progress in the fight against cancer. As a French biopharmaceutical company, we are deeply committed to fostering and enabling innovation in our home country. This collaboration is part of a broader effort to strengthen our ties within the scientific community, both in France and globally, with the goal of advancing the development of cutting-edge treatments for patients.” Nicolas MaesCEO, Orano Group“The success of Orano Med is an example of our group's ability to diversify beyond our core nuclear business. By applying our expertise in nuclear materials to fields like targeted alpha therapies, we are demonstrating that nuclear technology can have a positive societal impact, not just for energy and climate, but also for human health. This innovation reflects Orano's commitment to exploring new opportunities and taking bold steps to address some of the world’s most pressing challenges.” Sanofi’s investment will further strengthen Orano Med and allow the company to accelerate the development of its pipeline, leveraging its unique capabilities in the discovery and development of lead-212 based therapies. Orano Med has also developed a highly differentiating global industrial platform, which, thanks to its vast stock of raw materials and patented manufacturing process, will ensure an independent, reliable, and scalable supply of lead-212 based therapies to patients worldwide. Houman AshrafianExecutive Vice President, Head of Research and Development, Sanofi“We are thrilled to invest in the promising field of radioligand therapies, a modality that holds potential for patients suffering from rare 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.” Julien DodetPresident of the Governing Board, Orano Med “Sanofi’s partnership with Orano Med is a strong recognition of the potential of lead-212 based radioligand therapies to advance the treatment of cancers. This validates our strategy, having developed this expertise over the past 15 years, and reinforces our position as a leader in targeted alpha therapies. We look forward to combining Sanofi’s expertise with our R&D and world-class radiopharmaceutical capabilities to advance the development of potentially transformative therapies like AlphaMedix and make them available to patients in need as quickly as possible.” In striving to become a leading immunoscience company globally, Sanofi remains committed to advancing oncology innovation. The pipeline is being reshaped and prioritized, leveraging expertise in immunoscience to drive progress. Efforts are centered on difficult-to-treat cancers such as select hematologic malignancies and solid tumors with critical unmet needs, including rare cancers such as multiple myeloma, acute myeloid leukemia, and certain types of lymphomas, as well as gastrointestinal and lung cancers. Sanofi and Orano Med are members of the Paris Saclay Cancer Cluster and look forward to contributing to the ambitious agenda of the France 2030 plan to accelerate innovation in oncology. This agreement is subject to standard regulatory approvals required for transactions of this nature. Financial considerationsUnder the terms of the agreement, Sanofi will make an equity investment of €300 million, approximately 16% equity stake in the new entity valued at €1.9bn. About SanofiWe are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY About Orano MedOrano Med, a subsidiary of the Orano Group, is a clinical-stage biotechnology company that develops a new generation of targeted therapies against cancer using the unique properties of lead-212 (212Pb), an alpha-emitting radioisotope and one of the more potent therapeutic payloads against cancer cells known as Targeted Alpha-Emitter Therapy (TAT). The company is developing several treatments using 212Pb combined with various targeting agents. Orano Med has 212Pb manufacturing facilities, laboratories, and R&D centers in France and in the US and is currently investing to further expand its GMP-manufacturing capacities for 212Pb radiolabeled pharmaceuticals in North America and Europe. As a recognized international operator in the field of nuclear materials, Orano Group delivers solutions to address present and future global energy and health challenges. Its expertise and mastery of cutting-edge technologies enable Orano to offer its customers high value-added products and services throughout the entire fuel cycle. Every day, the Orano group’s 17,500 employees draw on their skills, unwavering dedication to safety and constant quest for innovation, with the commitment to develop know-how in the transformation and control of nuclear materials, for the climate and for a healthy and resource-efficient world, now and tomorrow. Contacts Orano MedSophie Letournel | +33 6 38 44 34 11| sophie.letournel@orano.group Orano GroupPress Office | +33 (0)1 34 96 12 15| press@orano.group Orano Investor relationsMarc Quesnoy | investors@orano.group Sanofi Media RelationsSandrine Guendoul | + 33 6 25 09 14 25 | sandrine.guendoul@sanofi.comEvan Berland | +1 215 432 0234 | evan.berland@sanofi.comNicolas Obrist | + 33 6 77 21 27 55 | nicolas.obrist@sanofi.comVictor Rouault | + 33 6 70 93 71 40 | victor.rouault@sanofi.comTimothy Gilbert | + 1 516 521 2929 | timothy.gilbert@sanofi.com Sanofi Investor RelationsThomas Kudsk Larsen |+ 44 7545 513 693 | thomas.larsen@sanofi.comAlizé Kaisserian | + 33 6 47 04 12 11 | alize.kaisserian@sanofi.com Sanofi forward-looking statementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions, and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successful, the future approval and commercial success of therapeutic alternatives, Sanofi’s ability to benefit from external growth opportunities, to complete related transactions and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic and market conditions, cost containment initiatives and subsequent changes thereto, and the impact that pandemics or other global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2023. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group apart from AlphaMedix. Attachment Press_Release