On December 14, 2021 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, reported a collaboration with Novartis in the form of a license agreement to develop, manufacture and commercialize DARPin-conjugated radioligand therapies (DARPin-RLTs) (Press release, Molecular Partners, DEC 14, 2021, View Source [SID1234597100]). The collaboration will combine Molecular Partners’ industry-leading ability to rapidly generate high-affinity DARPins and the RLT capabilities and expertise of Novartis.

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By harnessing the power of radioactive atoms and applying it to cancers through targeted radioligand therapy, RLTs have the potential to deliver molecularly targeted radiation to tumor cells anywhere in the body. Under the terms of the agreement, Molecular Partners will collaborate with Novartis to discover DARPin-RLTs that target specific tumor associated antigens. DARPins have great potential to enable robust, tumor-specific delivery of radioligands owing to their small size, allowing for greater tumor penetration, and high specificity and affinity.

"We are very pleased to announce this new collaboration with Novartis. For several years, the team at NIBR has established themselves as the world leader in the RLT field and working with them on this program is an easy choice to make," said Patrick Amstutz, CEO of Molecular Partners. "While DARPins can be designed to perform any number of biological tasks, here we highlight some of their innate characteristics, including small size and high specificity and affinity, which may offer an advantage to RLT’s which often require a highly specific delivery vehicle."

"Radioligand therapy is a transformative platform for delivering radiation to target cells, and DARPins are a unique modality for specifically targeting tumors," said Jay Bradner, President of the Novartis Institutes for BioMedical Research. "The marriage of these two technologies is designed to enable us to target radioligands directly to tumor cells anywhere in the body with the goal of improving and extending patients’ lives."

Under the agreement, both parties will collaborate on the discovery and optimization of the therapeutic candidates. Novartis would be responsible for all clinical development and commercialization activities. Novartis will pay $20 million upfront to Molecular Partners, total potential development, regulatory and commercialization milestone payments of up to $560 million, and up to low double-digit percent of royalties.

On December 14, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) a clinical-stage biotechnology company developing eganelisib, a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported it has been selected for addition to the NASDAQ Biotechnology Index (NASDAQ: NBI), effective as of market open on Monday, December 20, 2021 (Press release, Infinity Pharmaceuticals, DEC 14, 2021, View Source [SID1234597089]).

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The NBI is designed to track the performance of a set of securities listed on the NASDAQ Stock Market (NASDAQ), made up of NASDAQ-listed companies classified as Biotechnology & Pharmaceuticals by the Industry Classification Benchmark (ICB), and is widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. To be selected for addition to the NBI, a company must have a minimum market capitalization of $200 million; demonstrate an average daily trading volume of at least 100,000 shares; and must be Nasdaq-listed. The index is modified market capitalization-weighted such that constituents are capped at 8% (for the top 5) and at 4% (for the remaining) at each quarterly index rebalance; the entire index is reviewed and reconstituted annually in December.

"We are very gratified that Infinity’s progress has been recognized by the addition of INFI to the prestigious Nasdaq Biotechnology Index," said Adelene Perkins, Chief Executive Officer and Chair, Infinity Pharmaceuticals. "Our eganelisib data have continued to mature in very positive ways with presentations at SABCS and ASCO (Free ASCO Whitepaper) GU this year, demonstrating clinically meaningful outcomes in both metastatic triple negative breast cancer and urothelial cancer, respectively. Being included in this index is another important milestone as we continue to pursue bringing significantly better treatments to cancer patients."

For more information about the NASDAQ Biotechnology Index visit www.nasdaq.com.

On December 14, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported two data presentations, highlighted data from the UNITY-CLL Phase 3 trial evaluating the combination of ublituximab, the Company’s investigational anti-CD20 monoclonal antibody and UKONIQ (umbralisib), the Company’s inhibitor of PI3K-delta and CK1-epsilon, (U2), in patients with both treatment naïve and relapsed or refractory chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, DEC 14, 2021, View Source [SID1234597087]). Data presentations occurred yesterday evening during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "We are pleased to share two presentations last night at the ASH (Free ASH Whitepaper) annual meeting which included additional analyses of the UNITY-CLL Phase 3 trial evaluating the U2 combination in patients with both treatment naïve and relapsed or refractory CLL. We believe these presentations showcase the versatility of the U2 combination both by treatment subgroup, and also interestingly in a patient population generally characterized as unsuitable for BTKi-based therapy. While significant advances have been made in the treatment of CLL, there still remains underserved patients who may not be good candidates for or fail to respond to currently available treatments."

PRESENTATION HIGHLIGHTS

Poster Presentation Title: Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study

A total of 210 CLL patients were enrolled in the U2 cohort of the UNITY-CLL trial, including 119 treatment naïve and 91 previously treated.
Efficacy and safety highlights for the treatment naïve (TN) population included:
Independent review committee (IRC) assessed progression-free survival (PFS) of U2 in the TN population was 38.5 months, with two-year PFS of 76.6%
84% IRC-assessed overall response rate (ORR) in the TN population, including 5% complete response (CR)/complete response with incomplete marrow recovery (CRi)
Responses were durable with 76% maintaining response at 2 years
Grade 3/4 adverse events (AEs) of special interest occurring in the TN population included ALT elevation (12%), AST elevation (8%), rash (3%), pneumonia (7%), non-infectious colitis (3%), pneumonitis (1%) and opportunistic infections (1%).
Efficacy and safety highlights for the previously treated population (PT) included:
IRC-assessed PFS in the PT population was 19.5 months, with two-year PFS of 41.3%
82% IRC-assessed ORR in the PT population, including 4% CR/CRi
Responses were durable, with 43% maintaining response at 2 years
Grade 3/4 adverse events (AEs) of special interest occurring in the PT population included ALT elevation (3%), AST elevation (2%), rash (1%), pneumonia (11%) and opportunistic infections (1%).
Poster Presentation Title: Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

A total of 210 CLL patients were enrolled in the U2 cohort of the UNITY-CLL trial, including 119 treatment naïve and 91 previously treated.
131 (64%) of U2 treated patients had at least 1 comorbid condition or concomitant medication (conmed) that could pose potential issues with BTKi therapy.
88% ORR, including 5% CR, for those patients with at least 1 comorbidity or conmed (n=131), compared to 83% ORR, including 5% CR, for the entire U2 population (n=210).
No difference in IRC-assessed PFS was observed between the group of patients with at least 1 comorbidity or conmed compared to the entire U2 population (31.9 months for both groups).
Grade 3/4s AEs of clinical interest in the group of patients with at least 1 comorbidity or conmed and the entire U2 population respectively, included ALT elevation (8%, 8%), AST elevation (4%, 5%), non-infectious colitis (3%, 2%) and pneumonitis (1%, 0.5%).
The above referenced presentations are now available on the Publications page of the Company’s corporate website at View Source

On December 14, 2021 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy (RT) in cancer, reported that corrected results from its Phase 3 ROMAN trial of avasopasem for the treatment of RT-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) achieved statistical significance on the primary endpoint of reduction in the incidence of SOM. Avasopasem has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the reduction of SOM induced by RT (Press release, Galera Therapeutics, DEC 14, 2021, View Source [SID1234597086]).

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The Company previously announced the Phase 3 ROMAN trial of avasopasem in SOM did not achieve statistical significance on the primary endpoint. Upon further analysis, an error by the contract research organization (CRO) was identified in the statistical program. Correction of this error resulted in improved p-values for the primary and secondary endpoints.

The corrected p-values are as follows:

16% relative reduction in the incidence of SOM in the avasopasem treatment group (54%) vs. placebo group (64%) (p=0.0451*) (previously reported as p=0.113) (primary endpoint)
56% relative reduction in the number of days of SOM in the avasopasem treatment group (8 days) vs. placebo group (18 days) (p=0.0022*) (previously reported as p=0.011) (secondary endpoint)
27% relative reduction in the severity (incidence of Grade 4 OM) of SOM in the avasopasem treatment group (24%) vs. placebo group (33%) (p=0.052) (previously reported as p=0.167) (secondary endpoint)
The Company also announced topline results from its single-arm Phase 2a EUSOM trial of avasopasem in Europe for RT-induced SOM in patients with HNC undergoing standard-of-care RT + cisplatin. This trial was conducted in 12 centers across six countries in Europe and enrolled 38 patients, of which 33 completed full treatment. Avasopasem appeared to be generally well tolerated. In EUSOM, the incidence of SOM was 54.5% and the median number of days of SOM was 9 days, in line with the ROMAN trial in which the incidence was 54% and the median duration was 8 days.

"Given the high unmet medical need for patients with head and neck cancer who develop radiotherapy-induced severe oral mucositis, we are gratified that the Phase 3 ROMAN trial achieved statistical significance on the primary endpoint after the correction of the statistical programming error," said Mel Sorensen, M.D., President and CEO of Galera. "ROMAN is our second randomized trial conducted in patients with head and neck cancer to achieve statistical significance and demonstrate improved clinical benefit. As we continue to analyze the full data set and evaluate our resources, we look forward to meeting with the FDA in 2022 to discuss whether the results from this single Phase 3 trial together with the randomized Phase 2b trial could support an NDA submission."

Approximately 42,000 HNC patients undergo standard-of-care RT every year in the U.S. and are at risk of experiencing SOM, painful mouth sores that impact the ability to eat and drink. In market research, both radiation oncologists and patients cite SOM as the most burdensome RT toxicity in HNC treatment. Currently, there are no FDA approved drugs to reduce the incidence or duration of SOM in solid tumors.

Continued Dr. Sorensen, "In parallel, our anti-cancer therapeutic trials in lung and pancreatic cancer, which we refer to as the GRECO-1 and GRECO-2 trials, respectively, are currently enrolling, and we look forward to reporting initial data from our GRECO-1 trial in the first half of 2022. Both trials combine our second dismutase mimetic candidate, rucosopasem, with stereotactic body radiation therapy (SBRT) with the goal of augmenting the anti-cancer efficacy of SBRT."

Conference Call

Galera will host a conference call and live audio webcast on Tuesday, December 14 at 8:30 a.m. ET to discuss the ROMAN Phase 3 data, including additional analyses from the full data set, and provide a general business update. The webcast will be accessible from the Investors page of Galera’s website, investors.galeratx.com, and an archived version of the webcast will be available in the News & Events section of the Investors page of Galera’s website for 30 days following the event.

On December 14, 2021 OnKure, Inc., a clinical-stage biopharmaceutical company discovering and developing the next generation of oncology precision medicines, reported positive topline results from the first-in-human Phase 1 trial of OKI-179, the Company’s oral Class 1 histone deacetylase (HDAC) inhibitor (Press release, OnKure, DEC 14, 2021, View Source;utm_medium=rss&utm_campaign=onkure-therapeutics-announces-positive-topline-first-in-human-phase-1-results-for-oki-179 [SID1234597085]).

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The first-in-human Phase 1 dose-finding study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of escalating oral doses of OKI-179 in cancer patients. OKI-179 was shown to be safe and generally well-tolerated as a single agent using intermittent dosing schedules of either 4 days on/3 days off or 5 days on/2 days off for 21 days. The most common adverse events were nausea, fatigue and anemia. Nausea was manageable with antiemetics.

At doses of 120 mg and above, PK/PD data demonstrated robust target engagement, with exposures that were above the pharmacologically active concentrations observed in multiple preclinical, solid tumor models of RAS pathway mutated cancers. Results from this study indicate that 450 mg and 300 mg are the maximum tolerated doses for the 4 days on/3 days off and 5 days on/2 days off schedules, respectively.

"HDAC inhibitors have shown great promise, however they have little success treating solid tumors due to poor tolerability. We are extremely encouraged by these Phase 1 results and we believe OKI-179 can overcome the historic limitations, having demonstrated high levels of target engagement at two well-tolerated dosing schedules," said Tony Piscopio, Ph.D., Co-Founder, President and Chief Executive Officer of OnKure. "We look forward to investigating our promising selective HDAC inhibitor as a potential treatment for a wide range of solid malignancies."

"We are excited by the results of our first-in-human trial of OKI-179 that demonstrate a best-in-class selectivity and tolerability profile in an oral HDAC inhibitor," said Jennifer Diamond, M.D., Chief Medical Officer of OnKure. "Class 1 HDAC inhibitors have shown chemical synthetic lethality with RAS pathway inhibitors in cell-line and patient-derived tumor models that harbor mutations in the RAS pathway, driving increased cell death and tumor regressions."

Dr. Diamond continued: "With approximately 25-35% of all cancers having mutations in the RAS pathway, OKI-179 has the potential to change the treatment paradigm for many tumor types, potentially becoming a backbone therapy for all RAS mutated cancers in combination with a RAS-pathway inhibitor."

Based on these favorable results, the Company expects to initiate a Phase 1b/2 trial of OKI-179 in combination with binimetinib in patients with NRAS mutant melanoma where checkpoint inhibitor therapy has failed in the first half of 2022. This trial will initially evaluate safety, PK and PD of the combination and establish a recommended Phase 2 dose before initiating the open-label Phase 2 portion of the study.

About OKI-179
OKI-179 is a novel, oral Class 1 histone deacetylase (HDAC) inhibitor for the potential treatment of a wide range of solid and hematological malignancies. HDAC inhibitors have shown great promise in preclinical models, however they have had little success treating solid tumors, often due to poor tolerability, inappropriate dosing regimens, poorly conceived combinations, and a lack of stratifying biomarkers. OKI-179 is designed to have improved potency, selectivity, tolerability, as well as easy combinability to overcome the historic limitations of other HDAC inhibitors. OnKure is currently planning to conduct a Phase 1b/2 trial of OKI-179 in combination with binimetinib in patients with NRAS mutant melanoma in 2022.