On April 21, 2021 Cassava Sciences, Inc. (Nasdaq: SAVA), a clinical-stage biotechnology company focused on Alzheimer’s disease, reported financial results for the first quarter ended March 31, 2021 and guidance regarding the release of new clinical data with simufilam (Press release, Pain Therapeutics, APR 21, 2021, View Source [SID1234578308]). Simufilam is the Company’s lead drug candidate to treat Alzheimer’s disease.

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"Alzheimer’s is a progressive disease, so a patient’s cognition is expected to worsen over time," said Remi Barbier, President & CEO. "Patients’ cognition scores actually improved following 6 months of open-label treatment with simufilam. Showing similar drug effects following 9 months of open-label treatment would be remarkable, yet consistent with simufilam’s mechanism of action. Eventually, we’d like this drug candidate to benefit cognition for a year or longer."

In July 2021, Cassava Sciences plans to announce results of a pre-specified interim analysis that summarizes safety and cognition data on approximately the first 50 subjects to complete at least 9 months of open-label drug treatment. The Company will present these data July 26 – 29th at the 2021 Alzheimer’s Association International Conference (AAIC). AAIC’s scientific committee has invited the Company’s scientists to present the dataset as an oral presentation.

About the Open-label Study with Simufilam
In March 2020, Cassava Sciences initiated a long-term, open-label study to evaluate simufilam in patients with Alzheimer’s disease. This study is funded by a research grant award from the National Institutes of Health (NIH). The open-label study is intended to monitor the long-term safety and tolerability of simufilam 100 mg twice-daily for 12 months or longer in patients with Alzheimer’s disease. Another study objective is to measure changes in cognition on ADAS-Cog, a standard test of cognition in Alzheimer’s disease. The study’s clinical protocol has pre-specified cognition measurements at 6, 9 and 12 months.

The study’s target enrollment is approximately 150 subjects with mild-to-moderate Alzheimer’s disease (recently increased by 50 subjects). One-hundred subjects have enrolled in this study across multiple clinical sites in the U.S. and Canada.

On February 2, 2021, Cassava Sciences announced positive results of a first interim analysis that summarizes clinical data on the first 50 subjects to complete 6 months of open-label treatment. Patients’ cognition scores improved from baseline following 6 months of simufilam treatment, with no safety issues. Six months of simufilam treatment improved cognition scores by 1.6 points on ADAS-Cog11, a 10% mean improvement from baseline to month 6.

In September 2021, Cassava Sciences plans to announce results of an interim analysis that summarizes safety and cognition data on approximately the first 50 subjects to complete at least 12 months of open-label drug treatment.

About the Cognition Maintenance Study (CMS)
In June 2021, Cassava Sciences plans to initiate a double-blind, randomized, placebo-controlled study in patients with Alzheimer’s disease. Patients who have completed at least one year of open-label treatment with simufilam qualify to enroll in the Cognition Maintenance Study (CMS). Study subjects in the CMS will be randomized (1:1) to simufilam or placebo for six months. The CMS is designed to compare simufilam’s effects on cognition in Alzheimer’s patients who continue with drug treatment versus patients who discontinue drug treatment.

About the Phase 3 Clinical Program
Cassava Sciences plans to initiate a Phase 3 program of simufilam in Alzheimer’s disease in the second half of 2021. The Phase 3 program consists of two large, double-blind, randomized, placebo-controlled studies in patients with mild-to-moderate Alzheimer’s disease dementia.

Cassava Sciences’ first Phase 3 study is designed to evaluate disease-modifying effects of simufilam in Alzheimer’s disease. The goal is to demonstrate a slower rate of decline in cognition and health function in subjects treated with simufilam compared to placebo. Approximately 1,000 subjects to be enrolled, randomized (1:1:1) to simufilam 100 mg, 50 mg or placebo BID, and treated for 18 months. The co-primary efficacy endpoints are ADAS-Cog, a cognitive scale, and ADCS-ADL, a functional scale, both widely used clinical tools in trials of Alzheimer’s disease.

Cassava Sciences’ second Phase 3 study is designed to evaluate symptomatic improvement in Alzheimer’s disease. The goal is to demonstrate improved cognition and health function in subjects treated with simufilam compared to placebo. Approximately 600 subjects to be enrolled, randomized (1:1) to simufilam 100 mg or placebo BID, and treated for 12 months. The co-primary efficacy endpoints are ADAS-Cog, a cognitive scale, and ADCS-ADL, a functional scale.

Slide Deck
Cassava Sciences’ latest corporate presentation is available on its website under the Investors/Presentations page: View Source

Financial Results for First Quarter 2021
Net loss was $3.5 million, or $0.09 per share, compared to a net loss of $1.2 million, or $0.05 per share, for the same period in 2020. Net cash used in operations was $2.3 million during the first quarter of 2021.

Net cash use for operations for full-year 2021 is expected to be approximately $20 to $25 million. Cash and cash equivalents were $282.2 million as of March 31, 2021, with no debt.

Financial Highlights for First Quarter 2021

At March 31, 2021, cash and cash equivalents were $282.2 million, compared to $93.5 million at December 31, 2020, with no debt. Cash balance included net proceeds of approximately $189.8 million from the sale of 4.1 million shares of common stock completed February 2021. Cash balance also included $0.7 million from exercise of common stock warrants in the quarter. There were no remaining common stock warrants outstanding as of March 31, 2021.

Net cash used in operations during the quarter ended March 31, 2021 was $2.3 million, net of reimbursements received from NIH grant awards.

Research grant funding reimbursements of $0.6 million were received from NIH and recorded as a reduction in research and development (R&D) expenses. This compared to $1.3 million of NIH grant receipts received for the same period in 2020.

Net cash use for operations for full year 2021 is expected to be approximately $20 to $25 million, consistent with previous financial guidance. Net cash use in 2021 is expected to be driven by higher headcount and personnel expenses, manufacturing costs around large-scale drug supply, professional services expenses related to clinical programs, and operating costs such as insurance, office space and IT related expenses.

R&D expenses were $2.5 million. This compared to $0.5 million for the same period in 2020, representing a 365% increase. This increase was due primarily to costs related to manufacture of clinical trial supplies in anticipation of launching a Phase 3 clinical program in simufilam, increased personnel expenses, as well as a decrease in grant funding received from NIH compared to the prior year.

General and administrative (G&A) expenses were $1.0 million. This compared to $0.8 million for the same period in 2020, representing a 29% increase. This increase was due primarily to higher insurance costs and professional fees compared to the prior year.
About Simufilam
Simufilam is a proprietary, small molecule (oral) drug that restores the normal shape and function of altered filamin A (FLNA), a scaffolding protein, in the brain. Altered FLNA in the brain disrupts the normal function of neurons, leading to Alzheimer’s pathology, neurodegeneration and neuroinflammation. The underlying science for simufilam is published in peer-reviewed journals, including Journal of Neuroscience, Neurobiology of Aging, Journal of Biological Chemistry, Neuroimmunology and Neuroinflammation and Journal of Prevention of Alzheimer’s Disease. Cassava Sciences is also developing an investigational diagnostic, called SavaDx, to detect Alzheimer’s disease with a simple blood test.

Simufilam and SavaDx were both developed in-house. Both product candidates are substantially funded by peer-review research grant awards from the National Institutes of Health (NIH). 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.

About Alzheimer’s Disease
Alzheimer’s disease is a progressive brain disorder that destroys memory and thinking skills. Currently, there are no drug therapies to halt Alzheimer’s disease, much less reverse its course. As of 2020, there were approximately 50 million people worldwide living with dementia, a figure expected to increase to 150 million by 2050.1 The annual global cost of dementia is now above $1 trillion, according to Alzheimer’s Disease International, a charitable organization.

On April 21, 2021 Versant Ventures reported $950 million in additional capital allocated across a platform of three separate vehicles (Press release, Versant Ventures, APR 21, 2021, View Source [SID1234578394]). These included Versant Venture Capital VIII, a $560 million primary global biotech fund; Versant Voyageurs II, a $140 million booster fund; and Versant Vantage II, a $250 million later-stage opportunity fund.

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All three funds exceeded their initial targets and were heavily oversubscribed. The capital from existing investors and a select number of new top-tier limited partners will support Versant’s highly successful biotech investment strategy and portfolio construction model.

Versant Venture Capital VIII – primary global biotech fund

Fund VIII closed at $560 million and will be allocated to 20 or more biotechnology start-ups in the U.S., Canada and Europe. These newcos will be focused on translating breakthrough innovation into the next generation of therapeutics targeting the most important unmet medical needs. The emphasis will be placed on building sustainable companies that follow business models with dual paths to liquidity.

The fund will be deployed by the same team and will follow the same investment strategy that is consistently producing outlier returns. More specifically, Versant’s three predecessor funds are currently demonstrating top decile performance across the venture industry.

"The pace of scientific discovery and technology development in the healthcare sector continues to accelerate, including advances in engineering new cell and gene therapies, developing the next generation of antibodies and therapeutic proteins, and even conceiving novel small molecule constructs for previously intractable targets in the human proteome," said Brad Bolzon, Ph.D., chairman and managing director of Versant. "These innovations are at the heart of our investment model."

Versant expects the majority of Fund VIII portfolio companies to be created de novo by working directly with talented entrepreneurs or through the firm’s existing Discovery Engines that support about 60 scientists working in wet labs across North America and Europe.

Versant Voyageurs II – strategic booster fund

Versant Voyageurs II closed at $140 million and will co-invest with Fund VIII in a select number of Series A opportunities that show early potential to be breakout companies.

"During the course of constructing any given portfolio, we inevitably generate a select number of deals showing exceptional potential from the outset," said Dr. Bolzon. "In these circumstances, we now have the ability to access additional Versant capital beyond our typical Series A investment allocations to increase momentum."

Rather than extend Versant’s main fund and jeopardize reserves planned for other valuable portfolio companies, the Voyageurs II capital will be available to participate alongside those specific Series A rounds. Thus, Voyageurs II will serve as a booster fund for a handful of select deals.

Versant Vantage II – strategic opportunity fund

Versant Vantage II closed at $250 million and will primarily invest in Series B or later rounds of existing Versant portfolio companies that are nearing a liquidity event.

The remit of Vantage II is similar to its predecessor fund, Versant Vantage I, which was designed to provide later-stage investment opportunities in portfolio companies believed to be within 12 months of an exit.

"Vantage I launched in March 2019 and has exceeded expectations. Of the fund’s 15 later-stage commitments, there already are 11 liquid companies with an average time to IPO or M&A event of about six months," noted Dr. Bolzon. "We expect similar outcomes from Vantage II, which already has a deep lineup of potential Versant companies in which to invest."

Managing directors leading investments for the new funds include Dr. Bolzon, Jerel Davis, Ph.D., Alex Mayweg, Ph.D., Clare Ozawa, Ph.D., and Tom Woiwode, Ph.D.

On April 21, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company, reported the publication of "A phase 1 trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma" in the BMJ’s Journal for ImmunoTherapy of Cancer (Press release, Istari Oncology, APR 21, 2021, View Source [SID1234578290]). The results of this study suggest that PVSRIPO holds promise for patients with advanced melanoma refractory to both PD-1 inhibitors and BRAF-targeted therapy.1

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Twelve patients received 1, 2, or 3 intratumoral injections of PVSRIPO at 21-day intervals. Four of six patients (67%) who received 3 injections had an objective response, 3 of whom received anti-PD-1 therapy within 30 days prior, suggesting that PVSRIPO was able to initiate or rekindle immune responses in patients who have failed anti–PD-1 therapy. Responses were observed in both injected and noninjected tumors, suggestive of an abscopal response. These results are consistent with the findings from mechanistic studies that PVSRIPO generates a functional antitumor CD8+ T cell response capable of mediating effective, systemic antitumor immunity.2,3

Following study completion, 11/12 patients (92%) re-initiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up duration of 18 months. The antitumor responses observed suggest that PVSRIPO, either alone or in combination with anti–PD-1, may be an effective treatment in anti–PD-1 refractory melanoma.1

"The responses observed in patients with advanced disease, including in noninjected tumors in patients with significant in transit metastases, is potentially good news for the growing population of patients with unresectable melanoma who are refractory to anti–PD-1 and BRAF-targeted therapies," said Georgia Beasley, MD, Principal Investigator of the phase 1 study at Duke University. "These responses were observed without serious or dose-limiting toxicities."

"The responses seen in both injected and noninjected in-transit tumors with PVSRIPO are an important finding," noted Yana Najjar, MD, Assistant Professor of Medicine at the UPMC Hillman Cancer Center and Principal Investigator of the LUMINOS-102 phase 2 multicenter study (NCT04577807), which is investigating PVSRIPO alone and in combination with anti–PD-1 therapy and is now open to enrollment across the United States. "LUMINOS-102 will build on these data and further evaluate the ability of PVSRIPO to generate a systemic immune response that fights cancer in both injected and noninjected tumors and suppresses cancer growth over time in patients with unresectable anti–PD-1 refractory melanoma."

"The findings of this study are important further evidence of the therapeutic potential of PVSRIPO," said W. Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology. "PVSRIPO appears uniquely capable of engaging both innate and adaptive immune responses to generate antitumor immunity."

For more information about Istari Oncology and their ongoing clinical trials and research on PVSRIPO, visit istarioncology.com.

About PVSRIPO
PVSRIPO is an investigational immunotherapy based on the live attenuated Sabin type 1 poliovirus vaccine that has been genetically modified for safety. PVSRIPO has a distinct point of entry (the poliovirus receptor, CD155), which is expressed on virtually all solid tumors and antigen-presenting cells. Upon entry into the cell, PVSRIPO targets tumors via two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) generating innate and adaptive antitumor immune responses via nonlethal infection of antigen presenting cells in the tumor, which stimulates a specific signaling pathway resulting in a sustained, robust type-I/III interferon-dominant response, with minimal release of unwanted cytokines. Its effects are potentiated by prior vaccination against poliovirus. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma. PVSRIPO has also been granted Orphan Status by the FDA for advanced melanoma.

On April 21, 2021 Pacira BioSciences, Inc. (NASDAQ:PCRX) reported that it will report its first quarter financial results before the open of the U.S. markets on Tuesday, May 4, 2021 (Press release, Pacira Pharmaceuticals, APR 21, 2021, View Source [SID1234578309]). Following the release, the company will host a live conference call and webcast at 8:30 a.m. ET.

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To participate in the conference call, dial 1-877-845-0779 and provide the passcode 8238109. International callers may dial 1-720-545-0035 and use the same passcode. In addition, a live audio of the conference call will be available as a webcast. Interested parties can access the event through the "Events" page on the Pacira website at investor.pacira.com.

For those unable to participate in the live call, a replay will be available at 1-855-859-2056 (domestic) or 1-404-537-3406 (international) using the passcode 8238109. The replay of the call will be available for one week from the date of the live call. The webcast will be available on the Pacira website for approximately two weeks following the call.

On April 21, 2021 PerkinElmer, Inc., a global leader committed to innovating for a healthier world, reported that it is serving as a provider and co-developer of assays, instrument solutions and expertise for the PROXIDRUGS Consortium which is zeroing in on research for proximity drugs or PROTACs (PROteolysis Targeting Chimeras) (Press release, PerkinElmer, APR 21, 2021, View Source [SID1234578345]). PROTACs are a new class of drugs that take advantage of the body’s own cell protein recycling system to fight disease by tapping into the 80% of disease-relevant proteins that are currently untargeted by today’s available therapeutics. Led by Goethe University in Frankfurt, Germany, the Consortium includes researchers from the Technical University of Darmstadt, the Fraunhofer Institute for Translational Medicine and Pharmacology, and global pharmaceutical companies based in Frankfurt’s Rhine-Main region.

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The research project, starting October 2021, aims to streamline novel drug target validation by putting disease-relevant proteins in close proximity with key enzymes (such as E3 ligases) so that they can be marked for destruction and recycled by the cells’ natural shredding capabilities.

To help in these efforts, PerkinElmer will provide the consortium with no-wash AlphaLISA and HTRF immunoassay technologies and expertise in protein labeling as well as assay design; EnVision multimode plate readers; high content imaging technologies such as the Opera Phenix and Operetta CLS platforms; and data analysis and informatics tools like TIBCO Spotfire software. These PerkinElmer offerings will give PROXIDRUGS scientists a highly sensitive and accelerated discovery platform with rich data delivery and high throughput for both live and dead cell research.

Commenting on this groundbreaking research and collaboration, Alan Fletcher, SVP of Life Sciences at PerkinElmer said, "With only 20% of disease-relevant proteins currently being targeted by classical, small molecule drugs, new research approaches, such as PROTAC drug discovery, hold immense and exciting potential. We are delighted to be able to contribute our expertise and technologies to assist in the innovative work of the PROXIDRUGS Consortium as it seeks new ways to help unlock and tackle the vast majority of proteins behind widespread diseases such as cancer, neurological disorders, and cardiovascular, inflammatory and infectious conditions."

The PROXIDRUGS consortium is led by Ivan Đikić of Goethe University Frankfurt who also commented on the importance of forming alliances across organizations to help advance novel drug discovery and development, "Successful translation of biomedical research requires strong collaboration and convergence of industry and academic expertise. Our work with PerkinElmer within the PROXIDRUGS consortium is a good example of that. PerkinElmer’s expertise and innovation in assay development is of utmost importance and will help to create new insights for our discovery efforts."

The PROXIDRUGS Consortium was recently selected for funding by the German Federal Ministry of Education and Research as part of a highly competitive "Clusters4Future" competition.