On August 3, 2022 Kiniksa Pharmaceuticals, Ltd. (Nasdaq: KNSA) (Kiniksa), a biopharmaceutical company with a portfolio of assets designed to modulate immunological pathways across a spectrum of diseases, reported a global license agreement with Roche and Genentech, a member of the Roche Group (Genentech), for the rights to develop and commercialize vixarelimab, a fully human monoclonal antibody targeting oncostatin M receptor beta (OSMRβ) (Press release, Kiniksa Pharmaceuticals, AUG 3, 2022, View Source [SID1234617403]).

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"We are proud to have advanced vixarelimab from a preclinical-stage asset through Phase 2 clinical studies. Our work underscores the differentiated potential of the OSMRβ mechanism as well as its potential to help patients with serious unmet need," said Sanj K. Patel, Chairman and Chief Executive Officer of Kiniksa. "The agreement provides an optimal infrastructure for the further development of vixarelimab. We plan to allocate the non-dilutive capital received from this transaction towards synergistic opportunities across our portfolio, including the expansion of our ARCALYST cardiovascular franchise."

Under the terms of the global license agreement, Kiniksa will receive $100 million in upfront and near-term payments, and is eligible to receive up to approximately $600 million in certain clinical, regulatory, and sales-based milestones, before fulfilling upstream financial obligations. Kiniksa is also eligible to receive royalties on annual net sales. Genentech will obtain rights for the development and commercialization of vixarelimab. The transaction is subject to certain closing conditions, including the expiration of the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 and other customary closing conditions.

Genentech will focus development of vixarelimab in fibrosis, where oncostatin M (OSM)-mediated pathogenesis is thought to be an important pathway for intervention in multiple fibrotic indications.

"Pursuing novel therapies in fibrosis is central to Genentech’s focus on developing medicines for patients with respiratory diseases," said James Sabry, Global Head of Roche Pharma Partnering. "Developing vixarelimab, a first-in-class fully human monoclonal antibody, in fibrosis is another example of how we are taking an innovative approach to meet patients’ unmet needs."

Kiniksa has completed screening patients for the Phase 2b clinical trial of vixarelimab in prurigo nodularis. The company plans to complete the trial but will no longer disclose data in the second half of 2022.

On August 3, 2022 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported that the European Medicines Agency (EMA) issued a positive opinion on the Company’s application for orphan drug designation for tamibarotene for the treatment of myelodysplastic syndrome (MDS) (Press release, Syros Pharmaceuticals, AUG 3, 2022, View Source [SID1234617423]). Tamibarotene, an oral first-in-class selective retinoic acid receptor alpha (RARα) agonist, is currently being evaluated in combination with azacitidine in the SELECT-MDS-1 Phase 3 trial for RARA-positive patients with newly diagnosed higher-risk MDS (HR-MDS).

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Previously, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to tamibarotene in MDS in February 2022.

"We are pleased that the EMA has issued a positive opinion for orphan drug designation for tamibarotene as it represents an important milestone for MDS patients, who have an urgent need for effective, tolerable, and convenient treatment options," said David A. Roth, M.D., Syros’ Chief Medical Officer. "We believe tamibarotene has the potential to change the current standard of care and become the first therapy for a targeted population in HR-MDS. We continue to advance our SELECT-MDS-1 trial and are looking forward to announcing pivotal data in late 2023 or early 2024."

Orphan drug designation in the European Union (EU) is granted by the European Commission based on a positive opinion issued by the EMA Committee for Orphan Medicinal Products. The EMA’s orphan designation is available to companies developing treatments for life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 persons in the EU. Medicines that meet the EMA’s orphan designation criteria qualify for financial and regulatory incentives that include a 10-year period of marketing exclusivity in the EU after product approval, protocol assistance from the EMA at reduced fees during the product development phase and access to centralized marketing authorization.

The ongoing SELECT-MDS-1 Phase 3 clinical trial is evaluating the safety and efficacy of tamibarotene in combination with azacitidine for RARA-positive patients with newly diagnosed HR-MDS. Data from the pivotal trial are expected in the fourth quarter of 2023 or the first quarter of 2024, with a potential new drug application filing expected in 2024.

Syros is also evaluating tamibarotene in combination with azacitidine and venetoclax for RARA-positive patients with newly diagnosed unfit acute myeloid leukemia (AML), for which tamibarotene had previously received orphan drug designation from both the FDA and EMA. Data from the safety lead-in portion of the SELECT-AML-1 Phase 2 trial is expected in the second half of this year.

On August 3, 2022 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the second quarter of 2022 and provided a corporate update (Press release, Aclaris Therapeutics, AUG 3, 2022, View Source [SID1234617322]).

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"It has been a busy first half of the year as we continue in our pursuit of becoming a leading development-stage immunology company," said Dr. Neal Walker, Chief Executive Officer of Aclaris. "We have strengthened our senior leadership team this year with the addition of a number of accomplished leaders, including James Loerop, Chief Business Officer, Gail Cawkwell, MD, PhD, Chief Medical Officer, and most recently, Doug Manion, MD, President and Chief Operating Officer. During the second quarter we also were able to raise additional capital, which extended our expected cash runway to the end of 2025. We look forward to continuing to advance our clinical and pre-clinical programs as we move through the second half of the year."

Research and Development Highlights:

Clinical Programs

Zunsemetinib, an investigational oral small molecule MK2 inhibitor:
Currently being developed as a potential treatment for immuno-inflammatory diseases
Rheumatoid Arthritis (ATI-450-RA-202): This Phase 2b dose ranging trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses (20 mg and 50 mg twice daily) of zunsemetinib in combination with methotrexate in subjects with moderate to severe rheumatoid arthritis (RA) is ongoing. Aclaris continues to expect topline data in 2023.
Hidradenitis Suppurativa (ATI-450-HS-201): This Phase 2a trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of zunsemetinib (50 mg twice daily) in subjects with moderate to severe hidradenitis suppurativa (HS) is ongoing. Aclaris continues to expect topline data in the first half of 2023.
Psoriatic Arthritis (ATI-450-PsA-201): Aclaris initiated study activities in the second quarter in this Phase 2a trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of zunsemetinib (50 mg twice daily) in subjects with moderate to severe psoriatic arthritis (PsA). Aclaris continues to expect topline data in the first half of 2023.
ATI-1777, an investigational topical "soft" Janus kinase (JAK) 1/3 inhibitor:
Currently being developing as a potential treatment for moderate to severe atopic dermatitis (AD)
Atopic Dermatitis (ATI-1777-AD-202): This Phase 2b trial to determine the efficacy, safety, tolerability and pharmacokinetics of ATI-1777 in subjects with moderate to severe AD is ongoing. In this trial, Aclaris will explore multiple concentrations of twice daily treatment with ATI-1777 and a single concentration of once daily treatment with ATI-1777, in patients 12 years and older. Aclaris continues to expect topline data in the first half of 2023.
ATI-2138, an investigational oral ITK/TXK/JAK3 (ITJ) inhibitor:
Currently being developed as a potential treatment for T cell-mediated autoimmune diseases
ATI-2138-PKPD-101: This Phase 1 single ascending dose (SAD) trial to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of ATI-2138 in healthy subjects is ongoing. Aclaris continues to expect topline data in 2022.
If the Phase 1 SAD trial is successful, Aclaris currently plans to initiate a Phase 1 multiple ascending dose (MAD) trial of ATI-2138 in subjects with psoriasis in 2022. Aclaris is also currently exploring alternative indications that are relevant to the mechanism of action.
Preclinical Programs

ATI-2231, an investigational oral MK2 inhibitor compound:
Currently being explored as a potential treatment for pancreatic cancer and metastatic breast cancer as well as in preventing bone loss in patients with metastatic breast cancer
Second MK2 inhibitor generated from Aclaris’ proprietary KINect drug discovery platform and designed to have a long half-life.
IND-enabling studies are underway, and Aclaris expects to submit an IND by the end of 2022.
Financial Highlights:

Liquidity and Capital Resources

As of June 30, 2022, Aclaris had aggregate cash, cash equivalents and marketable securities of $256 million compared to $226 million as of December 31, 2021. Aggregate cash, cash equivalents and marketable securities as of June 30, 2022 included $73 million of net proceeds from the sale of 4.8 million shares under its ATM facility in April 2022.

Aclaris continues to anticipate that its cash, cash equivalents and marketable securities as of June 30, 2022 will be sufficient to fund its operations through the end of 2025, without giving effect to any potential business development transactions or additional financing activities.

Financial Results

Second Quarter 2022

Net loss was $20.5 million for the second quarter of 2022 compared to $18.2 million for the second quarter of 2021.
Total revenue was $1.5 million for the second quarter of 2022 compared to $1.8 million for the second quarter of 2021.
Research and development (R&D) expenses were $18.8 million for the quarter ended June 30, 2022 compared to $7.9 million for the prior year period.
The $10.9 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for a Phase 2b trial for RA, a Phase 2a trial for HS and a Phase 2a trial for PsA.
ATI-1777 development expenses related to drug candidate manufacturing and other preclinical activities and start-up costs associated with a Phase 2b clinical trial.
Preclinical development activities related to ATI-2231.
Compensation-related expenses due to an increase in headcount.
General and administrative (G&A) expenses were $6.1 million for the quarter ended June 30, 2022 compared to $5.9 million for the prior year period.
Revaluation of contingent consideration resulted in a $3.4 million reduction of expense for the quarter ended June 30, 2022 mainly due to higher discount rates, compared to a revaluation of contingent consideration expense of $4.8 million for the prior year period.
Year-to-date 2022

Net loss was $39.3 million for the six months ended June 30, 2022 compared to $46.9 million for the six months ended June 30, 2021.
Total revenue was $3.0 million for the six months ended June 30, 2022 compared to $3.6 million for the six months ended June 30, 2021.
R&D expenses were $33.1 million for the six months ended June 30, 2022 compared to $15.7 million for the prior year period.
The $17.4 million increase was primarily the result of higher:
Zunsemetinib development expenses, including costs associated with clinical activities for a Phase 2b trial for RA, a Phase 2a trial for HS and a Phase 2a trial for PsA.
ATI-1777 development expenses related to drug candidate manufacturing and other preclinical activities and start-up costs associated with a Phase 2b clinical trial.
Preclinical development activities related to ATI-2231.
Compensation-related expenses due to an increase in headcount.
G&A expenses were $12.2 million for the six months ended June 30, 2022 compared to $10.7 million for the prior year period.
The $1.5 million increase was primarily the result of higher compensation-related costs, including stock-based compensation, due to increased headcount and the impact of new equity awards granted during the six months ended June 30, 2022.
Revaluation of contingent consideration resulted in a $4.6 million reduction of expense for the six months ended June 30, 2022 mainly due to higher discount rates, compared to a revaluation of contingent consideration expense of $21.2 million for the prior year period.

On August 3, 2022 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that Bill Newell, Chief Executive Officer, will present at the 2022 Wedbush PacGrow Healthcare Conference’s panel discussion, "ADCs – Take Me to Your Tumor" on Wednesday, August 10, 2022, at 2:20 p.m. ET / 11:20 a.m. PT (Press release, Sutro Biopharma, AUG 3, 2022, View Source [SID1234617341]).

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The presentation will be accessible through the News & Events page of the Investor Relations section of the company’s website at www.sutrobio.com. An archived replay will be available for at least 30 days after the event.

On August 3, 2022 Cassava Sciences, Inc. (Nasdaq: SAVA), a clinical-stage biotechnology company focused on Alzheimer’s disease, reported financial results for the second quarter ended June 30, 2022, a mid-year corporate update, and interim clinical results of an open-label study with simufilam (Press release, Pain Therapeutics, AUG 3, 2022, View Source [SID1234617387]). Simufilam is Cassava Sciences’ lead drug candidate for the proposed treatment of Alzheimer’s disease. SavaDx is Cassava Sciences’ investigational diagnostic candidate to detect Alzheimer’s disease from a simple blood draw.

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"I’m pleased with our operating performance in the first half of 2022," said Remi Barbier, President & CEO. "I’m also humbled by the hard work of our team members and clinical partners. Persistence and a focus on performance are key when you’re trying to beat Alzheimer’s disease."

Update on Patient Enrollment for Phase 3 Program
A total of over 400 patients are now enrolled in our on-going Phase 3 program of simufilam in Alzheimer’s disease. Enrollment is almost evenly split between the two Phase 3 studies.

Overview of Phase 3 Program with Simufilam in Alzheimer’s Disease
Our Phase 3 program consists of two double-blind, randomized, placebo-controlled studies of simufilam in patients with mild-to-moderate Alzheimer’s disease. Both Phase 3 studies have Special Protocol Assessments (SPA) from the U.S. Food and Drug Administration. Both studies have the same co-primary efficacy endpoints: ADAS-Cog12 (a cognitive scale) and ADCS-ADL (a functional scale). A secondary efficacy endpoint for both studies is iADRS, a clinical tool that combines cognitive and functional scores from ADAS-Cog & ADCS-ADL. Patients are now being screened in clinical trial sites in the U.S., Canada, Puerto Rico and Australia.

RETHINK-ALZ is the trade name of our 52-week Phase 3 study. This randomized, double-blind, placebo-controlled study is designed to evaluate the safety & efficacy of oral simufilam 100 mg or placebo, twice daily, over 52 weeks in approximately 750 patients with Alzheimer’s disease.

REFOCUS-ALZ is the trade name of our 76-week Phase 3 study. This randomized, double-blind, placebo-controlled study is designed to evaluate the safety & efficacy of oral simufilam 100 mg, 50 mg or placebo, twice daily, over 76 weeks in approximately 1,000 patients with Alzheimer’s.

Future Open-label Extension Study for the Phase 3 Program
In the second half of 2022, we expect to initiate an open-label extension study for our Phase 3 program. This new study is designed to provide no-cost access to simufilam to patients with Alzheimer’s disease who have successfully completed a Phase 3 study of simufilam.

On-going Open-label Study with Simufilam in Alzheimer’s Disease
In March 2020, we initiated a long-term, open-label study to evaluate simufilam in patients with mild-to-moderate Alzheimer’s disease. The study is intended to monitor the long-term safety and tolerability of simufilam 100 mg twice daily over 12 months or more. This study has reached its target enrollment of approximately 200 patients. We expect all patients for this study will complete drug treatment in Q4 2022. We expect to announce top-line clinical results for this study approximately year-end 2022.

On-going Open-label Study – Interim Analysis on 100 Subjects at 12 Months
An interim analysis was conducted on the first 100 evaluable patients who completed at least 12 months of open-label treatment with simufilam 100 mg twice daily. Top-line results of this interim analysis show that from baseline to month-12:

Drug appears safe and well tolerated.
Overall ADAS-Cog11 scores improved an average of 1.5 points (S.D. ± 6.6; P<0.05)
63% of the 100 patients showed an improvement in ADAS-Cog11 scores, and this group of patients improved an average of 5.6 points (S.D. ± 3.8).
An additional 21% of the 100 patients declined less than 5 points on ADAS-Cog11, and this group of patients declined an average of 2.7 points (S.D. ± 1.4).
The 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog) was originally developed by the research community to measure cognitive impairment in patients with Alzheimer’s disease. ADAS-Cog is often used in clinical studies of patients with Alzheimer’s because it can help determine incremental improvements or declines in cognition over time.

Standard deviation ("S.D.") is a measure of how dispersed the data is in relation to the average. A low standard deviation generally shows the data are closely clustered around the average. A high standard deviation generally shows that the data is widely spread.

All clinical data from our open-label study are inherently exploratory in nature and, as with all open-label data, should be interpreted with caution. Data results from our open-label study does not constitute, and should not be interpreted as, evidence of therapeutic benefit for simufilam.

Cognition Maintenance Study (CMS) with Simufilam in Alzheimer’s Disease
In May 2021, we initiated a Cognition Maintenance Study (CMS). This is a double-blind, randomized, placebo-controlled study of simufilam in patients with mild-to-moderate Alzheimer’s disease. Study participants are randomized (1:1) to simufilam or placebo for six months. The CMS is designed to evaluate simufilam’s effects on cognition and health outcomes in Alzheimer’s patients who continue with drug treatment versus patients who discontinue drug treatment. To enroll in the CMS, patients must have previously completed 12 months or more of open-label treatment with simufilam.

The target enrollment for the CMS is 100 or more patients. Over 50 patients have now completed this study. Our goal is to complete patient enrollment for the CMS in Q4 2022. We expect to announce clinical results of the CMS approximately third-quarter 2023.

SavaDx
Our investigational product candidate, called SavaDx, is an early-stage program focused on detecting the presence of Alzheimer’s disease from a simple blood draw. SavaDx is currently designed as an antibody-based detection system for altered filamin A (FLNA) protein. Working with third parties, we continue to evaluate an innovative method to detect FLNA without the use of antibodies. For business, technical and personnel reasons, we continue to prioritize the development of simufilam, our novel drug candidate, over SavaDx.

Financial Update
Net loss for the second quarter 2022 was $19.3 million, or $0.48 per share, compared to a net loss of $5.1 million, or $0.13 per share, for the same period in 2021. Net cash used in operations was $34.6 million during the first six months of 2022. Net cash use for operations for full-year 2022 is expected to be approximately $80 to $90 million. Cash and cash equivalents were $197.2 million as of June 30, 2022, with no debt.

Financial Results for Second Quarter 2022

At June 30, 2022, cash and cash equivalents were $197.2 million, with no debt.
Net loss was $19.3 million, or $0.48 per share. This compares to a net loss of $5.1 million, or $0.13 per share, for the same period in 2021. Net loss increased compared to the prior period due primarily to a significant increase in our R&D activities for a Phase 3 program of simufilam in Alzheimer’s disease.
Net cash used in operations was $34.6 million during the first six months of 2022.
Net cash use in operations for full year 2022 is expected to be approximately $80 to $90 million.
Research and development (R&D) expenses were $16.9 million. This compared to $3.9 million for the same period in 2021. R&D expenses increased compared to the prior period due primarily to increased activities and expenses related to clinical and pre-clinical studies and support functions and personnel expenses.
General and administrative (G&A) expenses were $3.0 million. This compared to $1.2 million for the same period in 2021. G&A expenses increased compared to the prior period due primarily to increased activities and expenses related to legal services as well as depreciation and amortization.
About Simufilam
Simufilam (sim-uh-FILL-am) is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A (FLNA) protein in the brain. Cassava Sciences owns worldwide development and commercial rights to its research programs in Alzheimer’s disease, and related technologies, without royalty obligations to any third party.