On January 12, 2025 Tune Therapeutics (Tune) reported the completion of over $175M in financing led by New Enterprise Associates, Yosemite, Regeneron Ventures and Hevolution Foundation (Press release, Tune Therapeutics, JAN 12, 2025, View Source [SID1234649624]).

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"It is deeply gratifying to have seen this platform and company evolve so far," said Tune Co-Founder Dr. Charles Gersbach, whose research at Duke University formed the basis for Tune’s TEMPO epi-editing platform. "Tune has already achieved a global landmark in the field, in the clinical application of epi-editing to a common and chronic disease. Thanks to the support of our investors, we anticipate the development of many more new epi-editing therapies in the years to come."

The funding will accelerate the development of the company’s existing pipeline, currently anchored by Tune-401 – its clinical-stage epigenetic silencing drug for chronic Hepatitis B (HBV). It will also support the development of additional gene, cell, and regenerative therapy programs already underway at Tune, and to progress its broader mission of bringing the power and versatility of epigenetic therapies to bear on common and chronic diseases.

"We are incredibly proud to see Tune progress successfully into the clinic," said Reed Jobs, Founder and Investor at Yosemite. "The Yosemite team has been an enthusiastic backer of Tune from the beginning, as we feel that few technologies have the biological power of epigenetic medicine to transform disease outcomes for the better. The range of potential applications and indications is vast and will only continue to expand."

"To date, modern medicine and pharmacology has done much to extend our lifespans, but far less for our active healthspans," explains William Greene, Chief Investment Officer at Hevolution Foundation. "Chronic diseases of ageing are accelerating in incidence, prevalence, and severity, and current approaches are simply inadequate. It is our belief that epigenetic editing may prove to be the transformative modality we need to enable a new era of regenerative medicine."

Since its founding in 2021, Tune has made impressive strides in the development and application of its novel and potentially transformative epigenome editing platform. At the 2023 ASGCT (Free ASGCT Whitepaper) conference, Tune announced a global first in the field: the durable repression of a therapeutically relevant gene (PCSK9) in non-human primates using genetic tuning. This gene repression was accompanied by an enduring reduction of LDL cholesterol levels that is still ongoing almost 2 years after a single, transient delivery of the epi-silencing construct. Later that year, the company unveiled Tune-401, a first-in-class epigenetic silencer for chronic Hepatitis B, a condition that impacts over 250 million people, and is the leading cause of liver cancer worldwide.

In November of 2024, Tune announced it was moving to the clinical stage, having received approval to begin clinical trials in New Zealand, and subsequently in Hong Kong – supported by world-renowned hepatologists and Principal Investigators Dr. Ed Gane and Dr. Man-Fung Yuen, respectively. With its lead program now in the clinic, Tune is leveraging this momentum to enhance its platform capabilities and develop its other gene and cell therapy programs.

"With this renewed support, we are well-positioned to advance our HBV clinical program, to invest in our platform, and to expand our pipeline," said Akira Matsuno, Co-Founder, President and CFO of Tune Therapeutics. "We are grateful to all our investors for their deep confidence in our team and approach, backed by compelling data that continues to underscore the transformational potential of epi-editing as a therapeutic modality."

On January 12, 2025 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported an update on its programs, development plans and guidance on key milestones expected in 2025, to be presented at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco, California (Filing, Molecular Partners, JAN 12, 2025, View Source [SID1234649710]).

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"We are excited to enter 2025 with upcoming key value inflection points, on the Radio-DARPin side as well as Switch-DARPin and clinical T-cell engagers, to build on our achievements through 2024. Our recently expanded strategic partnership with Orano Med ensures us access to 212Pb, to arm our Radio-DARPins for up to 10 products. MP0712, our most advanced Radio-DARPin targeting DLL3, is moving into clinical development in 2025. Further, we have selected Mesothelin as the second target in the Orano Med partnership, with unique DARPin binders that only bind to juxtamembrane Meso while not being inhibited by the shed target," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

Molecular Partners has further strengthened and expanded its agreement with Orano Med for co-development of up to ten 212Pb-based Radio-DARPins. Molecular Partners holds commercialization rights to MP0712, which is the most advanced program, as well as the second nominated Radio-DARPin candidate, which targets the membrane-proximal portion of cell surface glycoprotein Mesothelin (MSLN). Orano Med will ensure the production of the 212Pb-based Radio-DARPins for clinical trials and commercialization. Further details on this second candidate are scheduled to be unveiled at the Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in Q2 2025.

Patrick Amstutz continued, "We are equally excited that our work on the MP0533 candidate in R/R AML is starting to yield encouraging results. As we work to implement our previously discussed protocol amendments, we are already starting to see patients benefit from treatment in our ongoing cohort 8, where we introduced an additional dosing timepoint early on. These preliminary data provide us with reassurance that our strategy to further densify early dosing has merit and could enable more patients to benefit longer from MP0533."

Cash and Cash Equivalents:
As of Dec 31 2024, Molecular Partners reports cash and cash equivalents of CHF 149 M (unaudited) and will provide full YE financial results on March 6, 2025.

Key current program status updates include:

MP0712 & Radio-DARPin pipeline

The Investigational New Drug (IND) application for MP0712, a 212Pb Radio-DARPin candidate against the tumor-associated protein delta-like ligand 3 (DLL3), is in preparation. Dialogue with the U.S. Food and Drug Administration (FDA) is ongoing and Molecular Partners and Orano Med anticipate submitting the IND application for MP0712 in H1 2025, with the first-in-human study to start following regulatory clearance.

The IND submission is being built, in part, on strong MP0712 preclinical results, including new in vivo data presented at the European Association of Nuclear Medicine Congress in October 2024 and the European Targeted Radiopharmaceuticals Summit in December 2024. MP0712 demonstrated high affinity and specificity for DLL3, which is a highly relevant target for radiopharmaceutical therapy. DLL3 has been shown to have homogeneous expression in tumors of patients with small cell lung cancer, and expression in healthy tissues is low.

The second Radio-DARPin program co-developed with Orano Med targets MSLN, which is overexpressed across several cancers with high unmet need, such as ovarian cancer, and largely absent from healthy tissues. The development of therapeutics against MSLN has been hampered by high shedding of MSLN. Leveraging the unique DARPin properties, Molecular Partners has developed Radio-DARPins able to selectively bind to the membrane-proximal portion of MSLN present on cells and are therefore not impacted by shed MSLN.

In addition to the above updates, Molecular Partners continues to progress its Radio-DARPin Therapy (RDT) portfolio of projects in partnership with Novartis and is evaluating additional targets for RDT programs.

MP0533 (multispecific T cell engager)

MP0533 is currently being evaluated in a Phase 1/2a clinical trial for relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome/AML (ClinicalTrials.gov: NCT05673057). Dose escalation in cohort 1–7 showed an acceptable safety profile and initial activity yet unsustained responses (four responders reported and encouraging blast reductions across additional patients), as presented in December 2024 at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting.

In the currently ongoing cohort 8, in which an additional early dosing timepoint was introduced to allow steeper and more frequent dosing to reach the MP0533 target dose faster, increased rates and depth of responses are being observed, with three out of the first eight evaluable patients demonstrating responses to-date (data cutoff 16 December 2024). Molecular Partners has submitted an amendment to the study protocol to improve the exposure profile of MP0533 and to further deepen and expand responses being observed in cohort 8. Data on the amended dosing scheme are expected in 2025.

MP0533 is a novel tetraspecific T cell engaging DARPin which simultaneously targets the three tumor-associated antigens (TAAs) CD33, CD123, and CD70, as well as CD3 on T cells. The mechanism of action of MP0533 is designed to preferentially kill AML cells that express at least two of the three TAAs while sparing healthy cells, which express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T cell engagement.

Switch-DARPin Platform (next-generation immune cell engagers)

Preclinical proof-of-concept in a solid tumor model for the novel T cell engager Switch-DARPin was presented at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November. The presented data provide further validation of Switch-DARPins showing that conditional Tcell activation with potent co-stimulation in solid tumors, but not in healthy tissues, is feasible.

Specifically, the CD3 Switch-DARPin molecule was shown to effectively induce potent tumor regression in vivo. Reduced cytokine release was observed in healthy tissues compared to tumor tissue. Cytokine release syndrome (CRS) is a significant toxicity event that has been observed with many T cell engagers in the clinic. As such, masking CD3 may prevent T cell activation in the absence of tumor antigens and allow for "silent" T cell engagers outside of tumors, thereby reducing the risk of CRS and providing a better safety profile to T cell engagers. In addition, co-engagement of CD2 led to sustained T cell activation and cytotoxic capacity, thereby enabling the development of potent T cell engagers with improved therapeutic window. Molecular Partners plans to present further in vivo data on the CD3 Switch-DARPin at the AACR (Free AACR Whitepaper) Annual Meeting in Q2 2025.

MP0317 (localized agonist)

Molecular Partners presented comprehensive biomarker analyses from the completed Phase 1 clinical trial of the CD40 agonist MP0317 in solid tumors at SITC (Free SITC Whitepaper) in November 2024. MP0317 is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts in the stroma of various solid tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated combination trials of MP0317 in 2025, in combination with immune checkpoint inhibitors and additional standard of care.

J.P. Morgan Presentation Details:

Presenter: Molecular Partners CEO Patrick Amstutz
Time: January 15, 2025, at 9:00 AM PST (6:00 PM CET)
Location: Westin St. Francis, Elizabethan A Ballroom, San Francisco, CA

A webcast will be accessible on the Molecular Partners website, under the Events tab.

On January 10, 2025 Labcorp (NYSE: LH), a global leader of innovative and comprehensive laboratory services, reported that the company will participate in a fireside chat at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, Jan. 14, at 3:45 p.m. (PT) (Press release, LabCorp, JAN 10, 2025, View Source [SID1234649593]).

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A live audio webcast of the fireside chat will be available via the Company Investor Relations website at ir.Labcorp.com and archived for replay.

On January 10, 2025 Verismo Therapeutics, a clinical-stage CAR T company developing novel KIR-CAR platform technology, reported that it has dosed the first patient in its CELESTIAL-301 Phase 1 clinical trial (Press release, Verismo Therapeutics, JAN 10, 2025, View Source [SID1234649610]). The patient was infused at Sarah Cannon Research Institute (SCRI) at Colorado Blood Cancer Institute (CBCI) in Denver, Colorado.

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CELESTIAL-301 aims to assess safety, tolerability, and preliminary efficacy of SynKIR-310 in patients with relapsed/refractory (r/r) B cell Non-Hodgkin Lymphomas (B cell NHL), including Diffuse Large B Cell lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), and Marginal Zone Lymphoma (MZL). The Phase 1 multicenter clinical trial is enrolling patients who previously received CAR T therapy but who have since relapsed or become refractory to it as well as patients who never received CAR T therapy.

CELESTIAL-301 trial seeks to address several areas of high unmet medical need. Commercially approved CAR T cell therapies have shown impressive high initial response rates in blood cancers. Over time, however, these therapies result in relapse in an estimated 40-50% of patients1. Such relapses are due in part to lack of long-term T cell effector function and persistence. There are currently very limited treatment options for patients with r/r DLBCL who relapse following treatment with commercial CAR T cell therapies.

SynKIR-310 relies on Verismo’s unique KIR-CAR platform and proprietary CD19 binder (DS191). SynKIR-310 targets CD19, similarly to the commercially approved CAR T therapies, with the added potential of prolonged anti-tumor T cell function and persistence. These KIR-CAR improvements may prevent early disease relapse in patients with advanced B cell lymphomas.

"The initiation of patient dosing in the CELESTIAL-301 trial marks an exciting milestone for Verismo Therapeutics as we advance our mission to develop transformative therapies for patients facing advanced lymphomas. CBCI’s commitment to patients and to conducting novel early-stage clinical trials has allowed us to reach this milestone earlier than expected," according to Dr. Laura Johnson, Chief Operations Officer and Chief Scientific Officer at Verismo Therapeutics. "SynKIR-310 is uniquely designed to prolong T cell functional persistence and combat the challenges of disease relapse, offering a potentially life-saving option for these patients."

"We are thrilled to administer this promising therapy," said Michael Tees, MD, the principal investigator at SCRI at Colorado Blood Cancer Institute (CBCI), where the first patient was dosed. "Emerging treatments like SynKIR-310 have potential to reshape care for patients with advanced lymphomas, offering new hope. This milestone showcases the impact of CBCI and other expert research centers in advancing early-stage clinical trials."

Verismo achieved IND clearance from the FDA in May 2024 to proceed with this multicenter Phase 1 clinical trial investigating SynKIR-310. SynKIR-310 is Verismo’s second clinical pipeline following SynKIR-110 targeting aggressive mesothelin-expressing solid tumors. For more information about the CELESTIAL-301 clinical trial, please visit ClinicalTrials.gov: NCT06544265.

On January 10, 2025 Ouro Medicines, a biotechnology company developing immune reset therapeutics for people living with chronic immune-mediated diseases, reported its launch with $120 million in funding (Press release, Ouro Medicines, JAN 10, 2025, View Source [SID1234656164]). The company was founded by Monograph Capital in partnership with GSK plc. The Series A was co-led by TPG Life Sciences Innovations, NEA, and Norwest Venture Partners, with participation from Monograph Capital, GSK, UPMC Enterprises, Boyu/Zoo Capital, LongRiver Investments, and other unnamed investors.

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Chronic immune-mediated diseases encompass an array of conditions where the body’s own immune cells play a driving role. This category includes B cell mediated diseases, which make up the company’s immediate focus. Current treatments for such diseases generally require ongoing immunosuppressive therapy and may be minimally effective with high levels of toxicity.

Due to their high potency, specificity, and relative ease of administration and manufacture, T cell engager antibodies (TCEs) have emerged as a promising off-the-shelf therapeutic modality for targeting and depleting specific pathogenic cell populations that drive immune-mediated diseases. By depleting target cell populations, TCEs might be used to reset the immune system to a state before those cells became pathogenic. This approach has potential to create long periods of remission where immunosuppression is unnecessary.

"We see a tremendous opportunity to define the future of treatment for people with immune-mediated diseases because the standard of care today leaves a lot to be desired," said Jaideep Dudani, CEO, Ouro Medicines and Portfolio Principal, Monograph Capital. "As a class, we believe TCEs have properties that make it possible to unlock immune system resets with periods of durable remission and without the need for ongoing immunosuppression. Being able to precisely target cell populations with a high-potency therapeutic is crucial to depleting whole lineages of pathogenic cell populations so that we can achieve immune reset."

Ouro’s most advanced product candidate is OM336, a BCMA-directed, bispecific T cell engager recently licensed from Keymed Biosciences (2162.HK). BCMA is highly expressed across several B cell subtypes that play a role in driving multiple indications where high specificity and potency are needed to achieve near-complete B cell depletion.

Keymed Biosciences is currently studying OM336 (CM336) in an ongoing Phase 2 expansion study in multiple myeloma in China. Ouro holds exclusive rights outside of Greater China and intends to start its first Phase 1 study in 2025. Examples of B cell mediated diseases include systemic lupus erythematosus, scleroderma, rheumatoid arthritis, Sjögren’s, and myositis. Supportive proof of concept data has been generated from the off-label use of BCMA-directed TCEs in these indications.

"TPG has been following the theme of deep B cell depletion since initial data came from CAR-T cell therapies," said Shinichiro Fuse, PhD, Business Unit Partner with TPG Life Sciences Innovations. "In Ouro, we found a leadership team and a group of advisors who bring deep knowledge of immune-mediated diseases and the key modalities being investigated for these indications, as well as a wealth of experience in both drug discovery and clinical development. We are thrilled to support the company as it works to develop immune reset therapeutics that address serious unmet needs for patients."

Behind its lead program, Ouro intends to advance a broad set of discovery programs targeting additional dimensions of B cell biology. These programs probe unique subsets of B cells compared to existing therapies in the clinic. Additionally, Ouro’s protein engineering expertise is being applied to next-generation versions of novel TCEs to continue to drive innovative treatments for chronic immune-mediated diseases.

"Monograph has high conviction that immune reset has the potential to change the course of many autoimmune diseases," said Tim Funnell, DPhil, Member, Ouro Medicines Board of Directors and Partner, Monograph Capital. "We started Ouro with an intention of building a discovery platform to unlock immune reset therapeutics, and we have been excited to accelerate the company’s development by bringing in OM336, which we believe has great promise based on the preclinical profile and clinical data we’ve seen in oncology. The combination of learnings from the OM336 clinical program and Ouro’s discovery activities will give us a strong foundation as we aim to build the leading immune reset therapeutics company."

Ouro has assembled a leadership team with expertise in a range of relevant diseases and modalities, including:

Jaideep Dudani, PhD, Chief Executive Officer. Dudani was most recently part of the founding team of Human Immunology Biosciences (HI-Bio), where he led portfolio development and strategy prior to the acquisition by Biogen, and has played cross-functional roles across R&D, strategy, and business development throughout his career. Dudani is also a Portfolio Principal at Monograph Capital.
Neely Mozaffarian, MD, PhD, Chief Medical Officer. Mozaffarian was previously Chief Medical Officer at GentiBio and Atomwise, with large pharma experience at Johnson & Johnson, Gilead, Eli Lilly, and AbbVie, leading drug development of biologics and small molecules.
Christina Carlson, JD, Chief Administrative Officer. Carlson most recently served as General Counsel of Human Immunology Biosciences (HI-Bio) and brings nearly 20 years of pharmaceutical and legal experience to her role at Ouro.
Kevin P. Baker, PhD, Chief Development Officer. Baker was previously Chief Development Officer at Pionyr Immunotherapeutics, where he led a team developing monoclonal antibodies and proteins to modulate the tumor microenvironment, and has deep experience across research programs in immune-oncology and immunology.
Ouro’s Board of Directors includes Shinichiro Fuse, PhD (TPG), Matt McAviney, MD (NEA), Brian Matesic, MD (Norwest), Tim Funnell, DPhil (Monograph), and Bo Chen, PhD (Keymed).

Supporting the Ouro leadership team are several deeply experienced clinical advisors, including John Davis, MD, MPH, President, Norte Health Consulting and former scientific advisory board member of HI-Bio; Matthew Baker, MD, MS, Clinical Chief in the Division of Immunology and Rheumatology at Stanford University and the Co-Director of the Stanford Multidisciplinary Sarcoidosis Program; and Stanford Peng, MD, PhD, most recently President and Head of Research & Development at Alpine Immune Sciences.