Prothena has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission .

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On February 28, 2023 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported that it will report its fourth quarter and full year 2022 financial results after market close on Tuesday, March 7, 2023 (Press release, Rigel, FEB 28, 2023, View Source [SID1234627874]). Rigel senior management will follow the announcement with a live conference call and webcast at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time) to discuss the financial results and give an update on the business.

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Participants can access the live conference call by dialing 877-407-3088 (domestic) or 201-389-0927 (international). The conference call and accompanying slides will also be webcast live and can be accessed from the Investor Relations section of the company’s website at www.rigel.com. The webcast will be archived and available for replay for 90 days after the call via the Rigel website.

On February 28, 2023 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Repare Therapeutics, FEB 28, 2023, View Source [SID1234627873]).

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"We made substantial progress advancing our innovative, synthetic lethality-based pipeline across multiple programs in 2022, including entering into a worldwide collaboration agreement with Roche to develop camonsertib, receiving Fast Track designation from the FDA for our first-in-class PKMYT1 inhibitor RP-6306, and advancing our preclinical programs," said Lloyd M. Segal, President and Chief Executive Officer of Repare." We expect 2023 to be another productive year for Repare across the portfolio, with early clinical readouts for both camonsertib and RP-6306 in the first half of 2023. In addition, we are poised to expand our pipeline leveraging our proprietary SNIPRx platform, and look forward to sharing more information on our third clinical program this summer."

2022 Highlights and 2023 Outlook:

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Advancing camonsertib, a potent and selective oral small molecule inhibitor of ATR (Ataxia-Telangiectasia and Rad3-related protein kinase) for the treatment of tumors with specific synthetic lethal genomic alterations in partnership with Roche.
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Initial data from the Phase 1/2 trials evaluating camonsertib in combination with three poly (ADP-ribose) polymerase (PARP) inhibitors is expected to be presented in the first half of 2023 at a major medical meeting.
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The Company expects to report initial data from the Phase 1/2 TRESR trial evaluating camonsertib in combination with gemcitabine in the summer or fall of 2023.
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Evaluating RP-6306, a first-in-class, oral PKMYT1 inhibitor as a monotherapy and in combinations in multiple early clinical studies.
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The Company expects to report initial Phase 1 clinical data for RP-6306 as a monotherapy for the treatment of molecularly selected advanced solid tumors (MYTHIC) in the first half of 2023. The Company expects to report initial Phase 1 clinical data for RP-6306 as a combination therapy for the treatment of molecularly selected advanced solid tumors in the fourth quarter of 2023.
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In the fourth quarter of 2022, the U.S. Food and Drug Administration (FDA) granted Fast Track designation (FTD) to RP-6306 in combination with gemcitabine for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated platinum resistant ovarian cancer. FTD is intended to facilitate the development and expedite the review of drugs to treat serious conditions and fulfill an unmet medical need, enabling drugs to reach patients earlier.
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Based on promising preclinical data released at the 34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium in October 2022, Repare is working with clinical investigators to initiate clinical testing, as part of an investigator-sponsored trial (IST), of a fourth new RP-6306 combination with carboplatin, with first patient dosing expected in the first half of 2023.

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In the fourth quarter of 2022, Repare entered into an agreement with Canadian Cancer Trials Group (CCTG) for a planned, basket Phase 2 IST to evaluate RP-6306 in patients with selected, advanced cancers receiving standard agents. A sub-study under the master clinical trial protocol will evaluate RP-6306 in combination with gemcitabine in patients with CD4/6i-resistant ER+/HER2- metastatic breast cancer.
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Advancing preclinical programs into clinical development.
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Repare expects to initiate IND-enabling studies in the first half of 2023 for a small molecule against an undisclosed target with potential to enter the clinic in late 2023 or early 2024, which represents an acceleration from the Company’s prior expectations for this program.
o
Repare is pursuing development of an inhibitor of polymerase theta (Polθ) in collaboration with Ono Pharmaceutical Company Ltd (Ono) in Japan, South Korea, Taiwan, Hong Kong, Macau and ASEAN countries, excluding mainland China. Repare retains all rights to develop and commercialize the products outside the Ono territory. In 2022, the Company selected a proposed inhibitor of Polθ, which it designated as RP-2119. In February 2023, based on its review of ongoing preclinical studies, Repare elected to prioritize other Polθ inhibiting compounds in its preclinical development portfolio, which it believes have a higher probability for clinical impact relative to RP-2119. The Company is now guiding toward clinical entry for a Polθ inhibitor in 2024.
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In January 2023, Repare received an approximate $1.5 million (¥200 million) milestone payment from Ono. The payment reflected the achievement of a research milestone under the Company’s research services, license and collaboration agreement with Ono (Ono Agreement).
o
Also in January 2023, Repare and Ono amended the Ono Agreement to further extend the research term until July 31, 2023. Previously, Repare had entered into an amendment with Ono in October 2021 to extend the research term by one year at no additional cost to Repare.
Fourth Quarter and Full Year 2022 Financial Results:

•
Cash and cash equivalents and marketable securities: Cash and cash equivalents and marketable securities as of December 31, 2022 were $343.9 million, which Repare believes will be sufficient to fund its planned operations into 2026.
•
Revenue from collaboration agreements: Revenue from collaboration agreements were $18.2 million and $131.8 million for the three- and twelve-month periods ended December 31, 2022, respectively, as compared to $6.9 million and $7.6 million for the three- and twelve-month periods ended December 31, 2021, due to revenue recognized from our collaboration and license agreement with Roche.
•
Research and development expenses, net of tax credits (Net R&D): Net R&D expenses were $29.9 million and $119.1 million for the three- and twelve-month periods ended December 31, 2022, respectively, as compared to $28.0 million and $90.0 million for the three- and twelve-month periods ended December 31, 2021 due to an increase in development activities related to the advancement of the RP-6306 program and preclinical activities related to pipeline programs; an increase of personnel-related costs, including share-based compensation, for increased headcount in support of discovery and development activities; and other research and development costs. Camonsertib costs were similar on a year over year basis and decreased quarter over quarter following the transfer of CMC related activities to Roche pursuant to the collaboration agreement.

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General and administrative (G&A) expenses: G&A expenses were $7.9 million and $32.6 million for the three- and twelve-month periods ended December 31, 2022, respectively, as compared to $7.6 million and $26.2 million for the three- and twelve-month periods ended December 31, 2021. The increase in G&A expenses for the three- and twelve-month periods were primarily due to higher personnel related costs, including share-based compensation; an increase in professional fees associated with the Roche collaboration agreement and the establishment of our at-the-market (ATM) offering, as well as timing of audit and SOX compliance efforts, partially offset by a decrease in our D&O insurance premium.
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Net loss: Net loss was $31.7 million, or $0.75 per share, and $29.0 million, or $0.69 per share, for the three- and twelve-month periods ended December 31, 2022, respectively, and $28.3 million, or $0.70 per share and $106.9 million, or $2.83 per share, for the three- and twelve-month periods ended December 31, 2021, respectively.
About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On February 28, 2023 PharmaMar (MSE:PHM) reported today total revenues of €196 million in 2022, compared with €229 million in the previous year (Press release, PharmaMar, FEB 28, 2023, View Source [SID1234627872]). This difference is mainly due to the non-recurring revenues recorded in 2021 and, to a lesser extent, to the change in regulations in France governing the prices of drugs made available through the compassionate access authorization (L’autorisation d’accès compassionnel, AAC) system. Of the total revenues generated by the Company, 92% originated outside of Spain.

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Of the total revenues recorded in 2022, recurring revenues (sales plus royalties), total €156.0 million compared with €164.8 million recorded in 2021.

Of the total recurring revenues in 2022, royalty revenues and raw material sales to our partners grew. Regarding the former, royalties increased 23% during 2022 to €50.3 million driven by sales of Zepzelca (lurbinectedin) in the US through our partner, Jazz Pharmaceuticals, reaching €46.9 million[1] (€38.0 million in 2021). Raw material sales of both Yondelis (trabectedin) and Zepzelca increased by 11.6% to €21.4 million at year-end.

The 5% period-over-period difference in total recurring revenues is mainly due to the change in revenues from Zepzelca in Europe under the compassionate access program and, to a lesser extent, the decrease in revenues from Yondelis sales as a result of the entry of generic products in the market in the last quarter of the year.

Revenues under the compassionate access program totaled €15.5 million at December 31st, 2022, compared with €30.2 million in 2021. It should be noted that this amount includes the impact of the entering into force in France of the regulations governing the prices of compounds available under the compassionate access authorization (L’autorisation d’accès compassionnel, AAC) system, under which lurbinectedin is distributed in that territory, and which has led to the application of significant discounts from the beginning of 2022.

Net sales of Yondelis amounted to €63.8 million through December 31st, compared with €69.4 million in the previous year. Although gross sales of Yondelis in Europe increased by 2% in 2022, price pressure, as a result of the entry of generic products into the European market is responsible for the 8% difference in net sales.

The Group’s non-recurring revenues, which are those from licensing agreements, totaled €40.2 million at year-end 2022, compared to €64.8 million at December 2021. In 2022, this revenue mainly corresponds to the income of €10 million in relation to Yondelis for the fulfillment of a commercial milestone, under the licensing agreement signed with Janssen (Johnson & Johnson) in 2001, and to the recognition in income of amounts received in 2020 as a result of the lurbinectedin licensing agreement with Jazz Pharmaceuticals ($300 million), amounts that are being recognized in the income statement depending on the degree of progress of the contractual commitments.

At December 31st, 2022, PharmaMar Group’s R&D expenditure amounted to €83.4 million, up 16% with respect to the previous year. This increase is due to the progression in the development of the different research areas. Thus, the oncology area accounted for the largest investment, with a total of €68.1 million, 12% more than in 2021. In 2022, the Company has launched up to 4 Phase III trials in the different therapeutic areas, including the LAGOON trial, which is the registration trial with Zepzelca for the treatment of relapsed Small Cell Lung Cancer. A new marine-derived anti-tumor compound, PM534, entered the clinic in 2022.

In 2022, R&D investment in the area of interfering RNAi also increased to €13 million, compared to €9.5 million in the previous year, as a result of the two phases III trials underway for the treatment of Dry Eye. In addition, a Phase II for the treatment of macular degeneration, among other developments, was initiated in this business area.

At the end of 2022, the PharmaMar Group had generated €38.3 million in cash from operating activities and had reduced total debt to €39 million. As a result, at December 31st, 2022, the group’s cash and cash equivalents position stood at €231.8 million, compared with €212.6 million at the end of the previous year, and net cash amounted to €192.8 million, 15% higher than at the beginning of the year.

On September 27th, the Board of Directors of PharmaMar Group decided to cease the activity of the diagnostics area, which was carried out through its wholly-owned subsidiary Genomica, S.A.U. Consequently, it agreed to initiate the corresponding procedures for the dissolution and liquidation of Genomica, S.A.U.

The PharmaMar Group will close 2022 with a net profit of €49.3 million as a result.

The Board of Directors of PharmaMar Group will propose to the Shareholders’ Meeting that a dividend of €0.65 gross per Pharma Mar, S.A. share be paid to shareholders against 2022 earnings.

On February 28, 2023 Cassava Sciences, Inc. (Nasdaq: SAVA), a clinical-stage biotechnology company focused on Alzheimer’s disease, reported financial results for the year ended December 31, 2022, and provided operating updates. Simufilam is Cassava Sciences’ oral drug candidate for the proposed treatment of Alzheimer’s disease dementia (Press release, Pain Therapeutics, FEB 28, 2023, View Source [SID1234627871]).

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"Setting aside headwinds, 2022 was highlighted by positive developments with patient enrollment in our Phase 3 clinical studies of simufilam in Alzheimer’s disease", said Remi Barbier, President & CEO. "Over 1,000 patients with Alzheimer’s are now enrolled in these two studies. By year-end 2023, we expect to reach our enrollment target of approximately 1,750 patients for the Phase 3 studies. Recently, we announced top-line results for an open-label study. In this study, over 200 mild-to-moderate Alzheimer’s patients were treated with simufilam for a year. Simufilam was well-tolerated, 47% of patients improved on ADAS-Cog scores over 12 months and an additional 23% of patients declined less than 5 points on ADAS-Cog. I believe these are noteworthy trial results, even as I am keenly aware that the gold standard in Alzheimer’s research requires results from randomized, controlled studies."

Alzheimer’s disease is a major public health issue. It imposes an immense burden on patients, their families and caregivers. Anti-amyloid antibody drugs that have received FDA approval are a step in the right direction. But by themselves, anti-amyloid drugs may not be enough for patients. Anti-amyloid drugs can slow cognitive decline modestly, but they can also cause brain bleeds in elderly patients, they require monthly trips to the local infusion center and periodical monitoring with MRI, they’re expensive and they lack Medicare coverage because they bypassed the full FDA approval process. Patients have waited many years for anti-amyloid drugs to be FDA-approved. Now that the wait is over, Cassava Sciences sees an even greater need to develop the next generation of innovative treatments, even if some of these potential treatments challenge scientific orthodoxy.

"It’s the spirit of innovation and our intense desire to help patients and their families that fuels our drive to develop simufilam as an oral drug candidate for people with Alzheimer’s disease," said Remi Barbier.

Cassava Sciences’ Scientific Goals for 2023

In Q2 2023, we expect to complete patient dosing for our on-going Cognition Maintenance Study, in which over 100 patients with mild-to-moderate Alzheimer’s disease are randomized (1:1) to simufilam or placebo for six months.
In Q3 2023, we expect to announce top-line results of the Cognition Maintenance Study.
In Q4 2023, we expect to complete patient enrollment for both of our Phase 3 studies.
Mid-year 2023, we expect an independent, third party to present evidential data for the biological activity of simufilam outside the field of neurodegeneration.
Mid-year 2023, we expect an independent, third party to generate new data for SavaDx using mass spectrometry.
Financial Highlights

At December 31, 2022, cash and cash equivalents were $201 million, compared to $233.4 million at December 31, 2021, with no debt. Year-end cash balance included net proceeds of $47.3 million from the sale of 1.7 million shares of common stock completed in November 2022.
Net cash used in operations full-year 2022 was $77.5 million, net of reimbursements received from National Institutes of Health (NIH) grant awards.
Net cash use for operations for the first half of 2023 is expected to be approximately $45 to $50 million, driven primarily by expenses for our clinical program in Alzheimer’s disease.
Research and development (R&D) expenses for the year ended December 31, 2022 were $68.0 million compared to $24.8 million for the same period in 2021. This increase was due primarily to costs to conduct the ongoing Phase 3 clinical program in simufilam, costs of an ongoing cognition maintenance study and open-label study in simufilam, and costs related to manufacture of clinical trial supplies, as well as increased pre-clinical study and personnel expenses compared to the prior year. These expenses are net of grant funding received from NIH, which is recorded as a reduction in R&D expenses.
Research grant funding reimbursements of $0.9 million were received from NIH and recorded as a reduction in R&D expenses. This compared to $3.9 million of NIH grant receipts received for 2021.
General and administrative (G&A) expenses for the year ended December 31, 2022 were $12.0 million compared to $8.1 million for 2021. This increase was primarily due to higher legal fees, personnel costs, insurance costs and depreciation and amortization as compared to 2021.
Ongoing Phase 3 Studies with Simufilam
Cassava Sciences is currently evaluating simufilam tablets for Alzheimer’s disease dementia in two Phase 3 clinical studies. These are randomized, double-blind, placebo-controlled trials. The Phase 3 program is recruiting a total of approximately 1,750 patients with mild-to-moderate Alzheimer’s disease who also meet other study eligibility criteria. Both Phase 3 studies have received a Special Protocol Assessment (SPA) from the U.S. Food and Drug Administration. The Phase 3 studies are actively recruiting Alzheimer’s patients in over 100 clinical sites in the United States, Canada, Puerto Rico, South Korea and Australia.

About Simufilam
Simufilam (sim-uh-FILL-am) is the chemical name for Cassava Sciences’ proprietary, small molecule (oral) drug candidate 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.