Alloy Therapeutics Unveils 2023 Innovation Roadmap Across Antibodies, TCRs, Bispecifics, and Genetic Medicines

On January 9, 2023 Alloy Therapeutics, a biotechnology ecosystem company, reported its 2023 roadmap of new discovery technologies and services across a range of biologic modalities (Press release, Alloy Therapeutics, JAN 9, 2023, View Source [SID1234626027]). Alloy will support its community of 140+ partners with deepened capabilities in its core antibodies offering, as well as substantial expansion into new modalities such as genetic medicines, leveraging an existing partnership announced with Dr. Sudhir Agrawal, a pioneer of gapmer antisense oligonucleotide (ASO) technology.

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Alloy launched in 2017 with a mission to centralize and democratize foundational technologies and expertise for biologics discovery to enable the global scientific community to advance the best, most innovative medicines more quickly. It started with the ATX-Gx transgenic humanized mouse platform for monoclonal antibody discovery and rapidly built antibody and bispecific discovery services around that foundational technology, along with novel protocols to serve collaborators with bespoke campaigns to discover the best therapeutic antibodies. Alloy reinvests 100% of its revenue into innovation and access to innovation, a commitment that enables the organization to continuously improve upon and develop new technologies to support its partners’ ambitious drug discovery goals.

In 2022, Alloy advanced into its second modality for T cell receptor-based (TCR-based) therapeutics, with the launch of Keyway TCR Discovery. Keyway is the first, and only, fully integrated discovery service provider and proprietary platform to discover therapeutic soluble proteins binding peptide-MHC complexes. Keyway is already collaborating in the discovery of highly specific TCR-mimic antibodies, and in 2023 will expand its end-to-end discovery offering to include soluble TCRs (alpha and beta chains). Keyway pairs TCR therapeutic pioneers with Alloy’s flagship bispecific antibody discovery and optimization services for the discovery of highly specific, next-generation soluble TCR-based therapeutics. Alloy’s ability to amalgamate shared capabilities such as antigen generation, bioinformatics, library design, protein engineering, antibody discovery, specialized specificity testing, and protein analytics across modalities enables it to quickly mobilize its scientists and collaborators into new areas for an expansive 2023 innovation roadmap.

"Our 2023 service and technology innovations are a reflection of years of thoughtful R&D work to give the drug discovery community access to the technologies and expertise that allow them to efficiently advance innovative therapeutics," said Alloy Therapeutics CEO and Founder Errik Anderson. "For some companies, ‘access’ to innovation is best served through working with our discovery services team in a collaborative and highly engaged process. Alloy is eager to serve our collaborators with bespoke discovery campaigns that allow them to discover the best drug against their therapeutic target, regardless of format."

2023 Innovations will span Alloy’s modalities:

Antibodies: Alloy’s foundational modality will advance new hyperimmune strains for its ATX-Gx monoclonal antibody discovery platform, available for license in partners’ labs or available as an end-to-end service as part of Alloy’s DeepImmune Antibody Discovery and Daedamab Antibody Discovery services. These groups will continue to strengthen their mission to find the best therapeutic antibodies with new capabilities such as machine learning-aided repertoire sequencing and protein optimization.
Bispecific Antibodies: Alloy will launch ATX-CLC, a new suite of transgenic common light chain mice to enhance the discovery of bispecifics, which will be integrated into bespoke discovery campaigns through DeepImmune Discovery at Alloy, as well as available for license.
Cell Therapy: Extending Alloy’s services in CAR-T generation, Alloy will launch the ATX-SiD transgenic humanized mouse for the discovery of single domain antibodies to enable development of bispecifics and chimeric antigen receptors. New discovery services supporting engineering into final CAR-T constructs as well as in vitro and in vivo functional screening will launch in 2023.

Keyway TCR Discovery: Keyway TCRm encompasses proprietary antibody-like bispecific formats for simultaneous effector cell engagement and target engagement and will launch new industry-leading specificity screening workflows to improve the safety profiles and drive the success of TCR-mimics in clinical trials.

Genetic Medicines: Alloy will launch Genetic Medicines Discovery services as its third fully integrated discovery services organization, leveraging proprietary platforms and world-class, modality-specific expertise. Through the collaboration with Dr. Agrawal, Alloy has developed proprietary technologies and oligonucleotide formats with differentiated properties compared to existing formats. Genetic Medicines will first partner with collaborators to convert existing gapmer antisense leads into these new formats for augmented activity and then launch its end-to-end de novo development of ASOs. This modality will also span immunostimulatory and immunosuppressive oligos, enabling collaborators to access unique sequences as proprietary adjuvant and autoimmunity drugs.

82VS: Alloy’s affiliated venture studio, 82VS, will be launching new companies advancing medicines discovered from the breadth of Alloy platforms and services. These startups are the first to validate and iterate on Alloy’s novel platform innovations and serve as great examples of what is possible for collaborators who would like to work with Alloy Discovery Services. In 2023, 82VS will launch new companies from stealth spanning TCR-mimics, bispecific antibodies, novel monoclonal antibodies, and genetic medicines.

"We are grateful to our partners who trust us with their biggest drug discovery challenges and provide the insights that lead to these technology advances," said Alloy Therapeutics President and Chief Scientific Officer Piotr Bobrowicz. "This type of collaboration is the reason Alloy started and will continue to drive the invention of foundational technologies to support sophisticated discovery campaigns across modalities to the benefit of the entire industry. We encourage drug discovery teams everywhere to look to Alloy as a partner to advance the technologies they need to be successful, through Alloy Research Services collaborations that can launch the discovery innovations of tomorrow."

A clear investment thesis

On January 9, 2023 Alkermes presented its corporate presentation (Presentation, Alkermes, JAN 9, 2023, View Source [SID1234626026]).

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Positive Results from Single Ascending Dose Phase 1 Study of ALE.F02 Targeting Claudin-1

On January 9, 2023 Alentis Therapeutics ("Alentis"), the biotechnology company developing breakthrough treatments for organ fibrosis and CLDN1+ tumors, reported positive results from a single ascending dose Phase 1 study of its lead program, ALE.F02, currently in development for the treatment of advanced kidney, lung and liver fibrosis (Press release, Alentis Therapeutics, JAN 9, 2023, View Source [SID1234626025]). The study found ALE.F02 to be well tolerated in healthy volunteers at all doses with a good safety profile and demonstrated initial evidence of on-target biological activity.

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CLDN1, one of the claudin family of transmembrane proteins like Claudin-18.2, is a previously unexploited target that plays a key role in the pathology of tumors with immune evasive properties and fibrotic diseases across multiple organs. Alentis is the only company developing potential treatments for solid cancers and fibrosis targeting CLDN1.

ALE.F02 is a highly selective anti-CLDN1 mAb that recognizes pathological overexpressed and conformation-dependent CLDN1 epitopes on transformed epithelial cells and is being investigated for the treatment of fibrotic disease in the kidney, lung and liver.

The Phase 1 clinical study was initiated in January 2022 to look at the safety and tolerability of ALE.F02 in 40 individuals comprising of five dose cohorts with eight individuals in each cohort. Dosing ranged from a minimum of 0.3mg/kg to a maximum of 20 mg/kg. Pharmacokinetic results predict an optimal dose for full receptor occupancy in humans within the range. No serious or severe adverse events were recorded. A multiple ascending dose Phase 1 study is ongoing, the results of which will be reported in Q1 2023.

Dr. Roberto Iacone, CEO at Alentis Therapeutics, commented: "These important clinical data for our lead program ALE.F02 are very encouraging, have enabled us to identify an optimal dose for further Phase 1 testing, and demonstrated encouraging on-target biological activity.

"As we continue to develop breakthrough treatments for solid cancers and fibrosis targeting CLDN1, we look forward to reporting the full Phase 1 results for ALE.F02 in Q1 2023. In addition, we expect to initiate a first-in-human clinical study of our lead oncology asset ALE.C04 in cancer patients in H2 2023."

Dr. Markus Meyer, VP R&D Operations at Alentis Therapeutics, added: "There are currently limited treatment options available for patients with fibrotic associated cancers and kidney, lung and liver fibrosis. CLDN1 is a novel, previously unexplored target with a unique mechanism of action in the pathology of CLDN1+ solid tumors and fibrosis. We continue to gather further clinical data as we develop a potential new treatment option for patients in the future."

A Commitment to address patients unmet needs

On January 9, 2023 Akebia presented its corporate presentation (Presentation, Akebia, JAN 9, 2023, View Source [SID1234626023]).

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Agios Unveils 2023-2026 Value-driving Catalysts Enabling Company’s Vision to Transform Patient Outcomes in Rare Diseases

On January 8, 2023 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported its anticipated 2023 milestones and significant value-driving catalysts through 2026 that support the company’s mission to transform patient outcomes in rare diseases (Press release, Agios Pharmaceuticals, JAN 8, 2023, View Source [SID1234626022]). Agios will present at the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11, 2023, at 7:30 a.m. PT, and a live webcast will be available at investor.agios.com.

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"Agios is poised for significant growth with the potential for approvals in two additional PYRUKYND indications by 2026, and is well capitalized to advance its robust existing clinical pipeline and expand its portfolio within our core areas of expertise," said Brian Goff, chief executive officer at Agios. "As the pioneering leader in PK activation with more than seven years of clinical experience with PYRUKYND, we have generated an impressive body of consistent and compelling data across rare hematological diseases with shared underlying pathophysiology that further builds confidence in our five ongoing pivotal clinical trials in thalassemia, sickle cell disease and pediatric PK deficiency. Furthermore, we are executing our first rare disease U.S. product launch with PYRUKYND in adult PK deficiency, providing the first disease-modifying therapy for this patient community that previously had no treatment options and building the capabilities to set us up for success with our expected launches in meaningfully larger patient populations."

Recent Highlights

Adult PK Deficiency: Received marketing authorization for PYRUKYND in adults with PK deficiency in the EU and Great Britain

Thalassemia: Enrolled approximately half of patients in the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND in not regularly transfused and regularly transfused adults with thalassemia, respectively

Sickle Cell Disease: Closed screening in the Phase 2 portion of the RISE UP study of PYRUKYND in adults with sickle cell disease in December and expect to complete enrollment in January

Data Presentations: Presented broad set of clinical and translational data at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, including long-term PYRUKYND data in adults with non-transfusion-dependent thalassemia and in adults with PK deficiency

Leadership: Appointed Tsveta Milanova to the role of chief commercial officer, bringing two decades of experience in rare disease commercial strategy and global market access

Anticipated 2023 Milestones

Thalassemia: Complete enrollment of the Phase 3 ENERGIZE and ENERGIZE-T studies of PYRUKYND by mid-year

Pediatric PK Deficiency: Enroll at least half of patients in the Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND by year-end

Sickle Cell Disease: Announce data readout from Phase 2 portion of RISE UP study of PYRUKUND and go/no-go to Phase 3 decision by mid-year

Lower-risk Myelodysplastic Syndromes (LR-MDS): Complete enrollment of Phase 2a study of novel PK activator AG-946 by year-end

Earlier-stage Pipeline: File investigational new drug (IND) application for PAH stabilizer for the treatment of phenylketonuria (PKU) by year-end

Agios 2026 Vision

By 2026, Agios’ vision is to establish a classical hematology franchise with PYRUKYND approvals across PK deficiency, thalassemia and sickle cell disease; expand its portfolio by advancing AG-946 and the preclinical pipeline as well as through disciplined business development aligned with the company’s core therapeutic focus areas and capabilities; and achieve cash-flow positivity. Agios provided a roadmap of additional significant potential catalysts between 2024 and 2026 to enable the realization of this vision, as follows:

2024

Data readout from Phase 3 ENERGIZE study of PYRUKYND in adults with non-transfusion-dependent thalassemia (first half of 2024)

Data readout from Phase 3 ENERGIZE-T study of PYRUKYND in adults with transfusion-dependent thalassemia (second half of 2024)

Data readout from Phase 2a study of AG-946 in LR-MDS

2025

Potential FDA approval for PYRUKYND in thalassemia

Data readout from Phase 3 portion of RISE UP study of PYRUKYND in sickle cell disease, pending go/no-go decision in 2023

Data readouts from Phase 3 ACTIVATE-kids and ACTIVATE-kidsT studies of PYRUKYND in pediatric PK deficiency

2026

Potential FDA approval for PYRUKYND in sickle cell disease

Potential FDA approval for PYRUKYND in pediatric PK deficiency

Achieve cash-flow positivity

Presentation at 41st Annual J.P. Morgan Healthcare Conference

Agios will webcast its corporate presentation from the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11 at 7:30 a.m. PT. A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.