On March 6, 2023 Congruence Therapeutics, a biotechnology company working at the interface of computational and experimental drug discovery to design novel small molecules for diseases of protein misfolding, reported the close of an extension to its Series A financing, bringing the total amount raised to over US$65 million (Press release, Congruence Therapeutics , MAR 6, 2023, View Source [SID1234648821]). This extension was led by new investor BDC Capital’s Thrive Venture Fund, with participation from current investors Amplitude Ventures, Fonds de solidarité FTQ, OrbiMed, Investissement Quebec (IQ), SilverArc, and others.

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"This financing provides further evidence of the emerging role that technology must play to drive innovation in biotechnology. We are proud to be pioneers in tech-enabled drug discovery with the support of high-quality investors who share our commitment to developing computational tools that will re-invent the way that drugs are discovered," said Dr. Clarissa Desjardins, CEO of Congruence. "These additional proceeds will allow us to accelerate our pace, advancing our Revenir platform and our pipeline of first-in-class and best-in-class programs for devastating genetic, rare and neurological diseases toward the clinic."

Michelle Scarborough, Managing Partner, Thrive Venture Fund at BDC Capital added, "With an incredible team led by Clarissa and a first-of-its-kind discovery platform, Congruence will quickly emerge as a leading biotechnology company who is well-positioned to disrupt traditional drug discovery and deliver real benefits to patients. We are proud to lead this investment round and look forward to supporting Congruence through its next phase of growth."

In February 2022, Congruence announced the close of its Series A financing of US$50 million, led by Amplitude Ventures and Fonds de solidarité FTQ, with participation from Lumira Ventures, Investissement Quebec, OrbiMed Advisors, Driehaus Capital Management, and others. Congruence Therapeutics was founded in 2021 by Clarissa Desjardins, Ph.D., previously the founder and chief executive officer of Clementia Pharmaceuticals, a company developing therapies for rare pediatric bone diseases and sold to Ipsen in early 2019 for US$1.3 billion. Clementia’s lead product, Sohonos (palovarotene), was recently approved in Canada and is under review at the FDA as the first treatment for Fibrodysplasia Ossificans Progressiva, a debilitating and progressive rare bone disorder. At Congruence, Dr. Desjardins has put into place a team of ‘drug hunters’ with experience in rare disease strategy and clinical development, computational chemistry, medicinal chemistry, and business development.

On March 6, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast and gynecological cancers harboring ESR1 mutations, reported that its lead drug candidate, lasofoxifene, improved vaginal/vulvar symptoms while fulvestrant worsened them in a study of postmenopausal women with locally advanced or metastatic estrogen receptor-positive (ER+)/HER2- breast cancer with an ESR1 mutation (Press release, Sermonix Pharmaceuticals, MAR 6, 2023, View Source [SID1234628340]).

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The results, derived from the open-label randomized Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE 1, NCT03781063) study, were shared March 4 in an e-poster presentation at the International Society for the Study of Women’s Sexual Health (ISSWSH) Annual Meeting 2023 in St. Louis.

Top-line data for ELAINE 1, which began enrollment in September 2019, were shared in September at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022. This secondary analysis aimed to investigate changes in vaginal/vulvar symptoms with lasofoxifene versus fulvestrant, as lasofoxifene improved symptoms of vulvovaginal atrophy (VVA) in two previous Phase 3 studies among postmenopausal women with moderate to severe VVA.

Vaginal/vulvar symptoms were evaluated in an exploratory analysis using the vaginal (VAS) and vulvar (VuAS) assessment scales, instruments validated in breast cancer patients to assess dryness, soreness, irritation, and pain.

Among patients who completed the VAS/VuAS at baseline, the mean composite VAS/VuAS score decreased (improved) from baseline to week 16 by 74% in lasofoxifene patients, but increased (worsened) by 36% in fulvestrant patients
In the subgroup of patients with ≥1 moderate/severe symptom(s) at baseline, mean composite VAS/VuAS score decreased from baseline to week 16 by 72% with lasofoxifene, in contrast to an increase of 32% with fulvestrant
The mean score for the most bothersome symptom decreased from baseline to week 16 by 65% with lasofoxifene versus 5% with fulvestrant
Of 103 enrolled patients, 75% of lasofoxifene patients and 65% of fulvestrant patients completed the VAS/VuAS at baseline; among them, 23% and 30% had ≥1 moderate/severe symptom(s), respectively
Women who completed the VAS/VuAS at baseline had a median age of 61.5 years
"This small-sample-sized exploratory analysis shows that lasofoxifene at 5 mg/day may potentially provide clinical benefits on vaginal and sexual health when treating metastatic breast cancer, though further studies are warranted to confirm such beneficial effects," said Shari B. Goldfarb, M.D., assistant attending physician, Memorial Sloan Kettering Cancer Center.

ELAINE 1 demonstrated that lasofoxifene, a novel targeted and tissue-selective oral endocrine therapy that acts as an ER antagonist at the breast, preliminarily prolonged median progression-free survival compared with fulvestrant (6.04 vs 4.04 months; P=0.138) in metastatic breast cancer patients with ESR1 mutations who had progressed taking a prior aromatase inhibitor (AI) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), with a favorable safety profile.

Novel therapies with positive impacts on vaginal health are desirable for breast cancer patients as estrogen-depleting AIs and degraders, and modulators of the estrogen receptor are associated with symptoms of genitourinary syndrome of menopause.

"Sermonix is pleased with the results of this study, which when combined with the primary ELAINE 1 findings as well as lasofoxifene’s well-researched history of improving vulvovaginal atrophy in postmenopausal women, demonstrate its potential as a novel therapy that clearly fills an unmet medical need," said Dr. David Portman, Sermonix founder and chief executive officer. "We look forward to further investigating lasofoxifene’s efficacy, as a treatment for metastatic breast cancer with fewer negative side effects that greatly impact patients’ quality of life."

About Lasofoxifene

Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with abemaciclib in phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On March 6, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on developing next-generation immunotherapies to address cancer immune resistance, reported it will host a virtual Key Opinion Leader (KOL) event on VISTA as an immuno-oncology target on Monday, March 20, 2023 at 10:00 AM ET (Press release, Kineta, MAR 6, 2023, View Source;utm_medium=rss&utm_campaign=kineta-to-host-key-opinion-leader-event-on-kva12123-vista-as-an-immuno-oncology-target [SID1234628335]).

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The event will feature immunology expert Michael A. Curran, PhD (MD Anderson Cancer Center Department of Immunology) who will discuss challenges in the current immuno-oncology landscape, along with the potential for VISTA blocking immunotherapy to address the problem of immunosuppression in the tumor microenvironment (TME), followed by a Fireside Chat with clinical oncology expert Patricia LoRusso, DO (Yale School of Medicine Cancer Center) on conducting clinical trials with novel immunotherapies to treat cancer.

Kineta’s leadership will provide an update on its lead program KVA12123, a novel anti-VISTA monoclonal antibody, as a treatment for patients with advanced solid tumors. Kineta recently initiated a Phase 1/Phase 2 clinical study to investigate KVA12123 alone and in combination with pembrolizumab, Merck’s anti-PD-1 therapy. A live question and answer session will follow the formal presentations.

To register for the event, please click here.

Michael A. Curran, PhD, received a PhD in Immunology from Stanford University where he was awarded the McDevitt prize for the best graduate thesis in his year. Dr. Curran was the first recipient of the prestigious American Cancer Society Levy Fellowship to fund his post-doctoral studies in the lab of Dr. James P. Allison. While pursuing his postdoctoral studies at Memorial Sloan-Kettering Cancer Center, Dr. Curran published several influential manuscripts describing how T cell co-stimulatory pathways could be modulated in tandem to mediate immunologic rejection of melanomas in mice. Dr. Curran was the first to describe how combination blockade of the T cell co-inhibitory receptors CTLA-4 and PD-1 promoted the rejection of a majority of murine melanomas – a combination that remains the most effective FDA-approved immunotherapy.

Patricia LoRusso, DO, is a Professor of Medicine (Medical Oncology) and Associate Cancer Center Director of Experimental Therapeutics at the Yale Cancer Center. She previously served in numerous leadership roles at Wayne State University’s Barbara Karmanos Cancer Institute, most recently as director of the Phase I Clinical Trials Program and of the Eisenberg Center for Experimental Therapeutics. Dr. LoRusso has served as co-chair of the NCI Cancer Therapy Evaluation Program Investigational Drug Steering Committee. She also served on the scientific committee of the AACR (Free AACR Whitepaper), and the education and scientific committees of ASCO (Free ASCO Whitepaper). She is a former editor of Investigational New Drugs, is currently on the editorial board for Clinical Cancer Research and is a reviewer for several journals.

On March 6, 2023 Achieve Life Sciences, Inc. (the "Company") reported that it has entered into a Cooperation Agreement (the "Cooperation Agreement") with Dialectic Capital Management, LP ("Dialectic") and related entities (collectively with Dialectic, the "Stockholders") regarding certain changes to the composition of the Company’s board of directors (the "Board") and other related matters (Filing, 8-K, OncoGenex Pharmaceuticals, MAR 6, 2023, View Source [SID1234628289]).

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Pursuant to the terms of the Cooperation Agreement: (1) the Company shall, no later than March 21, 2023, appoint three individuals (the "Designees") to the Board to fill three vacancies created by either (x) the departure of an incumbent member of the Board as designated in the Cooperation Agreement (the "Incumbent Directors") or (y) expanding the Board size to up to 11 directors; (2) the Board shall nominate the Designees for election at the 2023 Annual Meeting of the Company’s stockholders (the "2023 Annual Meeting"); (3) the Board shall appoint at least one of the Designees to each of the committees of the Board, other than the Chemistry, Manufacturing and Controls Committee, as well as any new committee(s) formed prior to the Expiration Date (as defined in the Cooperation Agreement); and (4) the Company shall set the Board size at eight directors no later than the date of the 2023 Annual Meeting (the "Incumbent Director Resignation Date") and, in the event there are more than eight directors serving on the Board as of the Incumbent Director Resignation Date, one or all of the Incumbent Directors, as applicable, shall submit his resignation to be effective no later than the Incumbent Director Resignation Date; provided, that in the event the resignation of any Incumbent Director as of Incumbent Director Resignation Date would cause any violation of the applicable listing rules of The Nasdaq Stock Market LLC, the parties agree that such resignation shall not be effective until such time as would ensure compliance with such listing rules and the parties shall work in good faith to document and approve such necessary modification(s) to the Incumbent Director Resignation Date.

The Cooperation Agreement further provides that if, at any time prior to the Expiration Date, any Designee (or any Replacement Designee (as defined below)) is unable or unwilling to serve and ceases to be a director, resigns as a director or is removed as a director, or for any other reason fails to serve or is not serving as a director, the Company and Dialectic shall work in good faith to promptly mutually agree upon a replacement candidate for appointment to the Board in substantially the same manner as the Company and Dialectic agreed upon the selection of such Designee (any such replacement nominee, when appointed to the Board, shall be referred to as a "Replacement Designee").

The Cooperation Agreement includes certain voting commitments, standstill, and mutual non-disparagement provisions (subject to certain carveouts and exceptions) that generally remain in place during the period beginning upon the execution and delivery of the Cooperation Agreement and ending on the earlier of (i) the date that is fifteen (15) business days prior to the notice deadline under the Company’s Sixth Amended and Restated Bylaws (and all amendments thereto) for stockholders to submit non-proxy access stockholder nominations of director candidates for election to the Board (the "Nomination Notice Deadline") at the 2024 Annual Meeting of the Company’s stockholders (the "2024 Annual Meeting"), (ii) the date the Stockholders, in the aggregate, cease to own at least 10% (on a non-converted basis) of the Company’s issued and outstanding common stock, (iii) any material breach of the Cooperation Agreement by any Stockholder or (iv) the last resignation of all three of the Designees; provided that notwithstanding anything to the contrary in the Cooperation Agreement, if (A) the Company confirms in writing that it will re-nominate the Designees for election as directors at the 2024 Annual Meeting or the 2025 Annual Meeting of the Company’s stockholders, as applicable (and that it will take such further actions as required by the Cooperation Agreement with respect to the Designees with respect to such annual meeting); (B) the Designees consent to such re-nomination(s); and (C) the Stockholders agree to the extension of the Expiration Date, then prong (i) shall be deemed to be automatically extended each such time until the date that is fifteen (15) business days prior to the applicable Nomination Notice Deadline(s) applicable to each such subsequent annual meeting of stockholders of the Company at which the Company has confirmed it will re-nominate the Designees.

The foregoing description of the Cooperation Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Cooperation Agreement filed as Exhibit 10.1 hereto.

On March 6, 2023 Isofol Medical AB (publ), (Nasdaq Stockholm: ISOFOL), reported that the company has decided to initiate a stepwise process to enable a cost-effective and risk-minimizing continued development of its drug candidate arfolitixorin (Press release, Isofol Medical, MAR 6, 2023, View Source [SID1234628288]). The company assesses that the planned activities, which are expected to be financed with existing funds, have the potential to bring arfolitixorin significantly closer to a market launch.

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The information in this press release is intended for investors.

Isofol´s drug candidate arfolitixorin has shown potential to improve the efficacy of the anticancer drug 5-FU – the basis of current standard treatment for colorectal cancer. Arfolitixorin is the first and only direct-acting folate-based drug candidate that enhances the anti-tumor effect of 5-FU without causing additional side effects. However, a recent Phase III study, AGENT, showed no statistically significant difference in efficacy between arfolitixorin and current standard treatment.

The strategic plan presented by Isofol Medical today aims to evaluate the result of the Phase III study in further detail. Based on the findings, the company will maximize the opportunities to take arfolitixorin further towards potential commercialization. The plan will be implemented in three steps.

Step 1: In-depth analyses of data from the phase III study
The company believes that further analyses of the extensive data generated in the Phase III study may provide greater clarity on possible reasons why arfolitixorin did not show a statistically significant difference in efficacy compared to the current standard of care in the study. One possible reason for the study outcome could be that the dose of arfolitixorin was not high enough to be comparable to the control group and/or was not administered in an optimal manner. The in-depth analyses of the Phase III study are expected to be completed in the second quarter of 2023.

Step 2: Laboratory study to document the effect of different doses
The next potential step is to initiate a time- and cost-effective laboratory study to document the effect of arfolitixorin in different doses and administration forms in combination with 5-FU. Such a study is expected to be initiated in the second quarter of 2023 and provide indicative information within approximately three months.

Step 3: A small clinical trial with a carefully selected dosing regimen
Assuming a positive outcome in the laboratory study, the company plans to conduct a small efficacy study in patients with a carefully selected dose and administration regimen. The results will be used as a basis for discussions with relevant pharmaceutical authorities regarding the further development plan, and may also increase the attractiveness of the project among potential licensees in the pharmaceutical industry. It is currently difficult to estimate the costs and time required for this type of efficacy study, but the company’s current assessment is that its existing financial means will be sufficient.

"We see great commercial potential for our drug candidate, but at the same time, it is in the nature of research that we cannot give any guarantees that the currently initiated development program will be successful. However, we promise to conduct our work in a scientifically professional manner, at a high pace and with strict cost control," says Mats Franzén, Chairman of the Board of Isofol.

Isofol has engaged several external specialists who will assist the company in the upcoming activities and evaluations of future scientific results, including Professor Anders Vedin (former CEO of Astra Hässle), Professor Bengt Gustavsson (colorectal surgeon, leading international researcher in the folate field and founder of Isofol Medical), Dr Rudolf Moser (formerly with Merck & Cie) and Dr Per Lindberg (specialist in patent strategies). In addition, the company will work closely with both the research organization at Sahlgrenska Östra Sjukhuset in Gothenburg which supported the original development of arfolitixorin, and with the international pharmaceutical company Merck & Cie, which developed the production process for the substance.

"I look forward to leading this step-by-step process with the long-term aim of providing cancer patients with access to an improved treatment based on Isofol Medical’s drug candidate. We are constantly prepared to reassess our plans based on the outcomes of the sequential activities and will of course continuously communicate the results in a transparent manner," says Thomas Andersson, Chief Executive Officer of Isofol.

For more information, please contact
Isofol Medical AB (publ)
Mats Franzén, Chairman of the Board
E-mail: [email protected]
Phone: +46 (0) 704 47 29 09

Thomas Andersson, Chief Executive Officer
E-mail: [email protected]

The information was submitted for publication, through the agency of the contact person set out above, at 10.00 CET, on March 6, 2023.