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CMTA and Addex Therapeutics Enter Collaboration to Advance GABA B PAM as Potential Treatment for CMT1A

On September 22, 2021 The Charcot–Marie–Tooth Association (CMTA), the largest philanthropic funder of CMT research worldwide, and Addex Therapeutics (SIX: ADXN and Nasdaq: ADXN), a clinical-stage pharmaceutical company pioneering allosteric modulation-based drug discovery and development, reported a collaboration to investigate a potential therapy for CMT type 1A (CMT1A), the most common subtype of the disease, which affects approximately 1.5 million people (Press release, Addex Therapeutics, SEP 22, 2021, View Source [SID1234590196]).

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The primary goal of the collaboration is to evaluate the benefit of Addex’s proprietary positive allosteric modulator’s (PAM’s) targeting the gamma-aminobutyric acid subtype B (GABAB) receptor in rodent models of CMT1A. The GABAB receptor has previously been shown to be instrumental in controlling the overexpression of Peripheral Myelin Protein-22 (PMP22) in a rat model of CMT1A. Elevated PMP22 is closely associated with the disabling peripheral neuropathy that accompanies CMT1A.

The CMTA’s Strategy to Accelerate Research (STAR) connects leading CMT clinicians and researchers with pharmaceutical partners committed to developing treatments and a cure for CMT. Strategic alliances with pharmaceutical partners like Addex Therapeutics support drug development efforts to deliver therapies to CMT patients.

"We are excited to establish this partnership with Addex Therapeutics as they work to advance their PAM’s to treat CMT1A," said CMTA’s CEO Amy Gray. "Strategic research partnerships with companies like Addex is a central part of our strategy to accelerate the development of treatments for the CMT community. Since launching STAR 12 years ago, the CMTA has been able to establish research partnerships with almost 40 pharmaceutical and biotech companies, and leading research labs around the world. We share Addex’s enthusiasm and passion for developing life-changing treatments for patients."

The research alliance with Addex will include joint study planning aimed at the chronic dosing of select GABAB PAM’s in rodent models of CMT1A, followed by detailed assessments aimed at measuring the improvement of key outcomes. These outcome measures include biomarkers, motor function, electrophysiology and peripheral nerve histology. This is made possible through the CMTA’s preclinical testing alliance: www.cmtausa.org/our-research/for-researchers/cmta-preclinical-testing-network/

"By combining the expertise of both the Charcot-Marie Tooth Association with our proven track record in the discovery and development of allosteric modulators, we aim to further understand how targeting GABAB with a positive allosteric modulator could benefit patients with CMT1A," said Tim Dyer, CEO of Addex Therapeutics. "As we move towards IND enabling studies, we look forward to working with the CMTA to build scientific evidence supporting our approach to tackle this tremendous unmet need."

IV BioHoldings Debuts Liquid Biopsy Portfolio; Partners with P4 Diagnostix to Scale Commercialization of Non-Invasive Lung, Liver and Breast Diagnostics

On September 22, 2021 IV BioHoldings (IVBH) reported the public launch of its bio innovation studio, debuting with a portfolio of three home-grown liquid biopsy companies, including LiquidLung, Inc., HepGene, Inc. and Mammogen, Inc. Collectively, the IVBH companies comprise eight clinical-ready diagnostics, spanning the care continuum for lung cancer, non-alcoholic fatty liver disease (NAFLD) and breast cancer, respectively (Press release, IV BioHoldings, SEP 22, 2021, View Source [SID1234590170]).

IVBH has also announced today its partnership with P4 Diagnostix (P4), a leader in diagnostic pathology, to fast-track commercial efforts of molecular diagnostic tests and meet clinical demand for earlier, easier and more precise detection, diagnosis and treatment of pulmonary, metabolic, and women’s health disease. Offering best-in-class testing services and proprietary healthcare informatics, P4 will serve as the exclusive laboratory partner for all clinical assay development and clinical validation across the lung cancer, NAFLD and breast cancer programs for each of the IVBH companies.

"What we’re seeing out of the IVBH ecosystem is platform test development capabilities that are years ahead of traditional test development in the liquid biopsy space, representing an opportunity for P4 to get on the ground floor of this dynamic area of molecular medicine," said Marcus Cognetti, Co-Founder of P4. "By partnering across the IVBH portfolio, we’re providing an industry-first opportunity to scale the speed and rate at which non-invasive diagnostics are made available to the millions of people for whom this testing is not available or are underserved by the existing standards of care. The novelty of the science, strength of the data, and competitive intellectual property built around these existing indications is quite astonishing, and is a testament to the efficiency of the IVBH business model and its progressive approach to R&D."

IVBH was founded in 2018 by Marty Keiser, with the vision of dramatically reducing the time, cost and risk associated with healthcare innovation through unique applications of data analysis using advanced technology. Its business model was purpose-built to accelerate value creation of novel intellectual property by allowing each of its disease-specific companies to leverage shared resources and tap into strategic partnerships formed by the studio.

In just over two years since launching LiquidLung, the first company to emerge from the studio, and one month after announcing the closing of a $2M seed round at its women’s health startup, Mammogen, the studio has now emerged from stealth with its portfolio of intellectual property positioned to address unmet clinical needs for 220 million Americans and over one billion people globally.1

IVBH partnered with Liquid Biosciences (LBS), whose Emerge bio-analytics platform has been radically reducing diagnostic and drug development time, cost and risk for a decade. IVBH and LBS collaborated on novel biomarker discovery and validation to develop the following liquid biopsy solutions:

LiquidLung, Inc. – Non-invasive early detection, confirmatory diagnosis, and histological typing and subtyping of lung cancer. In a study conducted in peripheral whole blood for lung cancer detection, the technology achieved 97% sensitivity, 85% specificity, including 100% detection of patients with stage I lung cancer, without the use of any demographics, clinical risk-factors, or radiological data.
HepGene, Inc. – Non-invasive early detection of NAFL, classification of NAFL versus non-alcoholic steatohepatitis (NASH), and definitive diagnosis of NASH. HepGene’s technology was validated across a diverse range of tissue types and biofluids (including blood), achieving 92% sensitivity, 97% specificity for early detection of NAFL and 94% sensitivity, 86% specificity for definitive diagnosis of NASH. The company IP also includes a proprietary portfolio of promising novel therapeutic targets for the treatment of NASH, which emerged from robust in vivo analysis of diseased patients and is supported by strong proof-of-principle that establish and validate biological plausibility.
Mammogen, Inc. – Non-invasive early detection and confirmatory diagnosis of breast cancer. Mammogen’s core technology, validated across peripheral blood mononuclear cells as well as saliva, is initially geared towards women under 40 and women over 55, two populations of women who are underserved by existing screening guidelines and current standards of care for breast cancer. Optimizing for women under 40, Mammogen’s technology achieved 93% sensitivity, 97% specificity. Optimizing for women over 55, the technology achieved 97% sensitivity, 87% specificity. Results were achieved without the use of any demographics or clinical risk-factors.
The introduction to P4 was made by Elizabeth Cormier-May, CEO of Mammogen and commercialization expert within the inner echelons of the IVBH studio, who has had a longstanding working relationship with the molecular lab throughout the course of her near twenty-year career in diagnostics.

"P4’s repeated success in diagnostic commercialization, seven CLIA certified laboratories strategically located across the US, and its proprietary IT solutions enabling electronic health record (EHR) integration, ensures that our clinical and commercial phases of development will be consistent with the efficiency of our model, making them the ideal partner for IVBH," stated Cormier-May.

"What normally takes the diagnostics industry at least six years to accomplish on a per product basis, we did for eight clinical-ready diagnostic products in just over two years," said IVBH founder and CEO Marty Keiser. "There’s no question that accelerated R&D timelines, and the corresponding reduction in risk associated with over 200 novel scientific discoveries across the lung, liver and breast programs, were a direct result of IVBH’s powerful partnership model and intentional application of exponential technologies such as that of our partners at LBS. With the addition of P4, we’re able to progress from R&D to commercialization with the level of speed, efficiency and quality that all human beings deserve."

IVBH is now scaling to support its flagship lung, liver and breast programs through clinical development and commercialization. Other plans on the horizon include a focus on pipeline expansion across pulmonary, metabolic and women’s health disease, and incubation of future company creations.

For more information on IV BioHoldings, visit www.ivbh.studio. To explore partnership opportunities, email [email protected].

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Onconova Therapeutics Announces Encouraging Clinical Data Supporting The Anti-Cancer Activity Of Rigosertib-Nivolumab Combination In Advanced KRAS+ Non-Small Cell Lung Cancer

On September 22, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported preliminary safety and efficacy data from an investigator-initiated Phase 1/2a trial of oral rigosertib plus the immune checkpoint inhibitor nivolumab in advanced KRAS mutated (KRAS+) non-small cell lung cancer (NSCLC) (Press release, Onconova, SEP 22, 2021, View Source [SID1234590169]). The data, which are being featured in a presentation at the 3rd Annual RAS Targeted Drug Development Summit, support the potential anti-cancer activity of rigosertib-nivolumab combination therapy in this indication and show that the doublet has been well tolerated to-date. Three quarters of patients enrolled in the trial have failed two or more lines of prior therapy and all have failed immune checkpoint inhibitors in various combinations.

Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, "The data being presented today support the potential applicability of rigosertib’s mechanism of action against multiple KRAS mutations and its synergy with immuno-oncology therapeutics. Radiographic responses were seen across multiple KRAS variants, which potentially differentiates rigosertib from other RAS pathway modulators that target particular KRAS mutations. These responses were observed at the primary tumor site as well as metastatic sites such as the pleura and bone. These results also suggest that rigosertib may augment the response to checkpoint inhibitors, which is consistent with observations from preclinical studies, with potential applicability to indications such as NSCLC, melanoma, and others. Looking forward, we will continue to leverage our investigator-initiated study program to advance rigosertib’s clinical development in high-need KRAS mutated indications while keeping our primary focus on our lead ON 123300 (narazaciclib) program."

Key data from the presentation include:

Demographics:

All enrolled patients (12/12) failed at least one line of prior therapy with a PD-1 checkpoint inhibitor (includes evaluable and non-evaluable patients)
9 of 12 (75%) enrolled patients failed at least two prior lines of therapy
Response Results:

2 of 7 (29%) evaluable patients achieved a partial response (PR)
PRs were observed in patients with two distinct KRAS mutations (G12C, G12V)
3 of 7 (43%) evaluable patients achieved disease control (PR or stable disease)
4 of 7 (57%) evaluable patients experienced progressive disease
Adverse Event Results:

The combination of rigosertib and nivolumab has been well tolerated and the maximum tolerated dose has not been reached to-date. Treatment related adverse events were mostly mild with two grade 3 adverse events.
3 patients discontinued study drug (2 grade 2 genitourinary toxicities, 1 dose limiting grade 3 hyponatremia)
No unexpected safety events or synergistic toxicities have been observed
"Combining rigosertib with the immune checkpoint inhibitor nivolumab has been well tolerated and notably led to partial responses in 29% of evaluable patients who had previously progressed on prior checkpoint inhibitor therapies," said Rajwanth Veluswamy, M.D., Assistant Professor, Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai and Principal Investigator of the trial. "This safety and early efficacy signal highlights the combination of rigosertib and nivolumab’s ability to target KRAS mutated NSCLCs and potentially overcome immune checkpoint inhibitor resistance mechanisms. Importantly, responses were seen with different KRAS+ variants, addressing a critical unmet need."

Mark S. Gelder, M.D., Chief Medical Officer of Onconova, commented, "We look forward to the continuation of this study and to continue development of the rigosertib nivolumab combination as a potential treatment for patients with limited therapeutic options."

Slides from the presentation titled, "Phase 1/2 Trial of Rigosertib & Nivolumab in KRAS-Mutated NSCLC in 2nd+ Line" will be available on the "Scientific Presentations" section of the Onconova website following the conference.

Webinar Featuring Expert Overview from Key Opinion Leaders
Onconova will host a webinar today, September 22, 2021, at 4:30 p.m. ET to discuss the preliminary Phase 1/2a data. The call will feature expert discussion with Dr. Veluswamy and Scott Antonia, M.D., Ph.D., Professor of Medicine at the Duke Cancer Institute and Director of its Center for Cancer Immunotherapy. A question and answer session with these experts will follow formal presentations by Dr. Veluswamy and members of the Onconova management team.

To attend the webinar, click here. A replay of the webinar will be available by visiting the investors and media page on Onconova’s website at www.onconova.com and clicking on the webcast link.

About the Investigator-initiated Phase 1/2a Trial
This Phase 1/2a trial is designed to evaluate the combination of rigosertib and nivolumab in advanced KRAS+ metastatic NSCLC patients who have progressed on standard of care with anti-PD-1 monotherapy or anti-PD-1 in combination with chemotherapy. It includes a dose-escalating Phase 1 portion followed by a Phase 2a dose-expansion portion. Patients in the trial receive oral rigosertib twice daily on days 1-21, and intravenous nivolumab on days 1 and 15 of 28-day cycles. The primary endpoints of the trial are safety assessments to determine maximum tolerated dose and overall response rate. Secondary endpoints include progression free survival and overall survival. For more information on the trial, see ClinicalTrials.gov Identifier: NCT04263090.

XOMA to Present at the 2021 Cantor Fitzgerald Virtual Global Healthcare Conference

On September 22, 2021 XOMA Corporation (NASDAQ: XOMA)’s Chief Executive Officer, Jim Neal, reported that it will present at the 2021 Cantor Fitzgerald Virtual Global Healthcare Conference on Tuesday, September 28, 2021, at 10:20 AM PT (Press release, Xoma, SEP 22, 2021, View Source [SID1234590168]).

Corvus Pharmaceuticals Provides Updates on Mupadolimab (Anti-CD73) Programs in Oncology and Infectious Disease

On September 22, 2021 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported an update on its development programs in oncology and infectious disease for mupadolimab (formerly CPI-006), a humanized monoclonal antibody directed against CD73 with a proposed dual mechanism of activating B cells to generate immune responses to viruses and tumor antigens, and inhibiting the production of immunosuppressive adenosine in the tumor micro environment (Press release, Corvus Pharmaceuticals, SEP 22, 2021, View Source [SID1234590167]).

Corvus is developing mupadolimab as a therapeutic for oncology indications and for infectious disease, starting with COVID-19. Today the Company announced results from its Phase 3 clinical trial of mupadolimab for COVID-19, which have been published online at medRxiv.org. The results, which cover 40 patients that were enrolled in the trial prior to its voluntary discontinuation, suggest improvement in the primary and key secondary endpoints in patients treated with single doses of mupadolimab at 2mg/kg and 1mg/kg compared to placebo. No drug related adverse events were reported in the trial.

"We believe the results from our Phase 3 Covid trial show the potential for a dose response effect on the primary endpoint of time to respiratory failure or death for the 2mg/kg and 1mg/kg mupadolimab cohorts compared to placebo. Secondary endpoints also favored the cohorts receiving mupadolimab. Most interestingly, antiviral responses in the 2mg/kg cohort trended higher across all variants tested, including delta. Cross reactivity to the delta variant is of interest as patients were enrolled prior to its emergence as the dominant variant in the United States," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "As expected when we discontinued the trial, statistical significance was not reached due to the sample size. However, we are very encouraged by the consistent trends and immune response data, which we believe support mupadolimab’s proposed mechanism of action and its potential value for the treatment of viral infections. Combined with the findings in our previous Phase 1 trial in 29 patients, we believe there is mounting evidence that mupadolimab could become a universal treatment for viral diseases, with the ability to address immune escape from variants. We plan to evaluate our next steps with mupadolimab for COVID-19 as we continue to analyze the trial data and explore partnership opportunities to continue its development as a therapeutic."

Mupadolimab also is currently being studied in a Phase 1b/2 clinical study in patients with HPV+ oropharyngeal cancers and non small cell lung cancers (NSCLC) that have failed previous treatment with anti-PD-1 therapy and chemotherapy. Data from the Phase 1b/2 clinical study has been accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November.

"Mupadolimab is one of the most studied anti-CD73 antibodies and is uniquely positioned with a potential dual mechanism, B cell activation and inhibition of immunosuppressive adenosine production," said Dr. Miller. "The complementary mechanisms could result in enhanced immune responses to viral antigens and to tumor antigens. We believe this will enable a unique approach to treating cancers, that can benefit both from removing the adenosine-mediated blockade of the immune system and enhancing immune responses through B cell activation. We look forward to presenting new data from our Phase 1b/2 oncology study at the SITC (Free SITC Whitepaper) meeting in November."

Mupadolimab for COVID-19 Trial Results
This was a randomized, double blind placebo-controlled trial design. In July, Corvus discontinued the clinical trial, which had planned to enroll approximately 1,000 patients, due to positive trends exhibited by COVID-19 vaccines in lowering serious infection and hospitalizations at that time. The discontinuation was not related to any safety or efficacy issues observed in study patients and occurred prior to the recent surge in COVID-19 cases and before the dominant emergence of the delta variant. Of the 40 patients enrolled prior to the discontinuation, 15 received the mupadolimab 2mg/kg dose, 14 received the mupadolimab 1mg/kg dose, and 11 received placebo. Treatment arms were well balanced, except for the 2mg/kg cohort, which had patients with more severe disease on admission with 60% on non-invasive ventilation or high flow oxygen devices, compared to 7% in the 1mg/kg cohort and 27% in the placebo cohort. Data from the three cohorts remained blinded until the final analysis.

The primary endpoint of the clinical trial was the proportion of patients progressing to respiratory failure or death during the 28 days after dosing. In the 2mg/kg cohort, 93.3% of patients were alive and free from respiratory failure, compared to 85.7% in the 1mg/kg cohort and 81.1% in the placebo. The results in the placebo control group were in line with results reported in other randomized trials. In addition, positive trends favoring mupadolimab treatment compared to placebo were seen for all the key secondary endpoints, including time to clinical improvement, time to sustained clinical improvement and time to hospital discharge.

MUPADOLIMAB 2MG/KG AND 1MG/KG VS. PLACEBO
(all received standard of care treatment)

2 MG/KG + SOC
(N=15) 1 MG/KG + SOC
(N=14) PLACEBO + SOC
(N=11)
PRIMARY ENDPOINT:
Free from Respiratory Failure or Death (%) 93.3 85.7 81.1
SECONDARY ENDPOINTS:
Median Days to Improvement (95% CI) 7.0 (4-9) 5.5 (3-14) 11.0 (2-14)
Median Days Sustained Improve (95% CI) 8.0 (4-12) 6.0 (3-14) 11.0 (2-21)
Median Days to Discharge (95% CI) 6.0 (4-12) 4.0 (2-5) 7.0 (2-12)

The results also included anti-viral antibody responses for 26 patients for which pre-treatment and day 28 blood serum are available (8 from the 1mg/kg cohort, 11 from the 2mg/kg cohort and 7 from the placebo cohort). Serum titers in the 2mg/kg cohort appeared to trend higher against the original COVID-19 strain and variants (alpha (B.1.1.7), beta (B.1.351), gamma (P.1) and delta (B.1.617.2), with several patients exhibiting very high titers. Patients in the 2mg/kg cohort demonstrated higher cross-reactivity with the beta, gamma and delta variants compared to 1mg/kg and placebo.