On November 6, 2023 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported financial results for the quarter ended September 30, 2023, and highlighted recent corporate accomplishments (Press release, Zentalis Pharmaceuticals, NOV 6, 2023, View Source [SID1234637049]).

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"We are executing on our fast-to-market strategy for our potentially first-in-class and best-in-class WEE1 inhibitor, azenosertib, while also laying the groundwork for the franchise opportunity we see for azenosertib across multiple tumor types," said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. "Azenosertib continues to show very encouraging monotherapy anti-tumor activity, safety and tolerability in both ovarian cancer and uterine serous carcinoma. We are executing our clinical strategy to advance this high-potential asset to patients with ovarian cancer and uterine serous carcinoma as quickly as possible and expand into additional indications where WEE1 inhibition has the potential to improve outcomes for patients. By focusing our team and resources on the advancement of azenosertib, Zentalis is targeting the submission of the first NDA for azenosertib in a gynecologic malignancy in 2026."

"This quarter we are also executing on our succession plan for Chief Scientific Officer, which will see our Chief Translational Officer, Mark Lackner, succeed our co-founder, Kevin Bunker, at the end of the year" said Dr. Blackwell. "Kevin’s passion for discovering promising oncology drugs is a cornerstone of our culture and led to four of our product candidates advancing into the clinic, including azenosertib. I want to thank Kevin for his immense contributions to Zentalis and to the cancer patients we serve."

"Since joining Zentalis last year, Mark has put together a talented translational team and has spearheaded our biomarker enrichment strategies for azenosertib," continued Dr. Blackwell. "Mark’s appointment as Chief Scientific Officer sees our translational and discovery efforts brought under a single umbrella, which puts us in a strong position as we continue to advance azenosertib through the clinic while supporting robust preclinical drug discovery efforts."

Program Updates and Highlights

•Azenosertib monotherapy program. Today, the Company announced an updated analysis of the ongoing Phase 1 clinical trial of azenosertib as a monotherapy in solid tumors (ZN-c3-001), which continued to show anti-tumor activity with intermittent dosing. In the same population of 19 platinum resistant or refractory ovarian cancer and uterine serous carcinoma (USC) patients that were included in the data reported on June 6, 2023, the objective response rate (ORR) was 37%.

Median follow-up has increased by nearly 5 months and the median progression free survival (mPFS) has increased to 6.5 months. With additional safety-evaluable patients and follow-up since June, azenosertib continues to demonstrate a favorable safety and tolerability profile that is similar to or better than approved ovarian cancer products, supporting its continued advancement

•Azenosertib development strategy. Azenosertib is currently being evaluated in more than 10 ongoing and planned clinical trials as a monotherapy and in combinations with compelling scientific rationales across a broad array of tumor types. The Company is on track to submit its first New Drug Application (NDA) for azenosertib in a gynecologic malignancy in 2026. The Company has revised its strategy in platinum sensitive ovarian cancer (PSOC) and plans to evaluate azenosertib in PSOC in the first-line (1L) maintenance setting in the clinic. This strategy allows for the opportunity to benefit a larger segment of patients with ovarian cancer and fill a gap in the treatment paradigm since the standard of care in the 1L maintenance setting is evolving and fewer options are available. The Company plans to provide additional details on this trial in the second half of 2024, and anticipates initiating enrollment in 2025.

•Presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference: Ovarian Cancer. In October, the Company presented a poster presentation titled "Cyclin E1 Positive Staining Is Frequent and Independent of Prior Platinum Treatment in High Grade Serous Ovarian Cancer" at the AACR (Free AACR Whitepaper) Special Conference: Ovarian Cancer in Boston. To review the data in more detail, click here.

•ZN-d5 + azenosertib in relapsed or refractory acute myeloid leukemia (R/R AML). Zentalis is the only company known to have both a WEE1 inhibitor, azenosertib, and a BCL-2 inhibitor, ZN-d5, in clinical development. The Company is evaluating the combination of these promising product candidates in a Phase 1/2 trial in heavily pretreated patients with R/R AML based on strong preclinical data demonstrating highly synergistic anti-leukemia activity of this combination. The Company updated guidance for sharing initial data from this trial to the second half of 2024.

•ZN-d5 in relapsed or refractory light chain amyloidosis (R/R AL amyloidosis). Dose escalation is complete in the Phase 1 trial of ZN-d5 as a monotherapy in R/R AL amyloidosis. A preliminary efficacy signal was observed in patients with R/R AL amyloidosis with a hematologic response rate of 40% in patients treated with at least 400 mg daily of ZN-d5. ZN-d5 was well tolerated with few treatment-related adverse events. The proposed monotherapy dose has been identified as 800 mg daily. The Company does not plan to develop ZN-d5 further for this indication in order to focus its resources on the azenosertib franchise opportunity, including the azenosertib + ZN-d5 combination.

Corporate Highlight

•Today, the Company announced that Mark Lackner, Ph.D., Chief Translational Officer, Head of Biomarker Strategy, will succeed co-founder, Kevin Bunker, Ph.D., as Chief Scientific Officer at the end of the year. Dr. Bunker will continue his service to the Company as an advisor following the transition. Dr. Lackner joined Zentalis in October 2022. Prior to Zentalis, Dr. Lackner served as Senior Vice President, Head of Biology and Translational Sciences at IDEAYA Biosciences, where he successfully led biology efforts contributing to three small molecule development candidates and established a strong translational team that led to the discovery of a novel combination biomarker strategy. Previously, Dr. Lackner worked at Genentech for over a decade, holding multiple roles of increasing responsibility that culminated in serving as the Head of Genentech Oncology Early Stage Biomarker Group. During this tenure, he led multiple

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research teams in developing and incorporating predictive biomarker strategies across all phases of clinical trials and managed a diverse biomarker portfolio spanning targeted therapies, immuno-oncology agents and antibody drug conjugates.

Anticipated Upcoming Milestones

•1H 2024
◦Final results of Phase 1 azenosertib + chemotherapy (gemcitabine) trial in osteosarcoma (ZN-c3-003)
•2H 2024
◦Final results of Phase 1b azenosertib monotherapy trial in solid tumors (ZN-c3-001)
◦Topline data from Phase 1/2 azenosertib + PARP inhibitor (niraparib) and azenosertib monotherapy trial in platinum resistant ovarian cancer in partnership with GSK (MAMMOTH, ZN-c3-006)
◦Initial data from Phase 1 azenosertib + BEACON regimen (encorafenib + cetuximab) trial in BRAF mutant metastatic colorectal cancer in partnership with Pfizer (ZN-c3-016)
◦Initial data from Phase 1 of azenosertib + ZN-d5 trial in R/R AML (ZN-d5-004C)
◦Additional details on planned clinical trial of azenosertib in PSOC in the 1L maintenance setting
•1H 2025
◦Topline data from Phase 2 azenosertib monotherapy trial in platinum resistant high-grade serous ovarian cancer (DENALI, ZN-c3-005)
•2H 2025
◦Topline data from Phase 2 azenosertib monotherapy trial in recurrent or persistent USC (TETON, ZN-c3-004)
•2025
◦Initiate clinical trial of azenosertib in PSOC in the 1L maintenance setting.
•2026
◦First NDA for azenosertib in a gynecologic malignancy

Third Quarter 2023 Financial Results

•Cash and Marketable Securities Position: As of September 30, 2023, Zentalis had cash, cash equivalents and marketable securities of $516.6 million. The Company believes that its existing cash, cash equivalents and marketable securities as of September 30, 2023 will be sufficient to fund its operating expenses and capital expenditure requirements into 2026.

•Research and Development Expenses: Research and development (R&D) expenses for the quarter ended September 30, 2023 were $46.8 million, compared to $42.2 million for the quarter ended September 30, 2022. The increase of $4.6 million was primarily attributable to $3.2 million of costs shared with Zentera in the prior period, a $2.6 million increase related to personnel expenses, of which $1.4 million related to non-cash stock-based compensation expense, and $0.8 million related to consulting costs. These increases were partially offset by decreases of $1.3 million and $0.7 million in facility expenses and clinical expenses, respectively.

•General and Administrative Expenses: General and administrative (G&A) expenses for the quarter ended September 30, 2023 were $16.0 million, compared to $12.0 million during the quarter ended September 30, 2022. This increase of $4.0 million was primarily attributable to a $2.9 million increase in personnel expenses, of which $2.2 million related to non-cash stock-based compensation expense, and a $1.1 million increase related to facilities and outside services.

About Azenosertib
Azenosertib is a potentially first-in-class and best-in-class small molecule WEE1 inhibitor in development for the treatment of cancer. Inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death. Currently, there are no FDA-approved WEE1 inhibitors, and azenosertib has been designed for superior selectivity and pharmacokinetic properties. Azenosertib is being developed in therapeutic areas of high unmet need and is being evaluated as a monotherapy, in combination with chemotherapy, and in combination with molecularly targeted agents.

On November 6, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported final clinical and immunobiological data from the Phase 1/2 clinical trial of galinpepimut-S (GPS) in combination with pembrolizumab (Keytruda) in Wilms’ tumor-1 (WT1)-positive platinum-resistant ovarian cancer (NCT03761914) (Press release, Sellas Life Sciences, NOV 6, 2023, View Source [SID1234637048]).

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Results are being presented in an e-poster session by Roisin E. O’Cearbhaill, M.D., Research Director, Gynecologic Medical Oncology Service; Clinical Director, Solid Tumor, Cellular Therapy Service; and Associate Attending Physician at Memorial Sloan Kettering Cancer Center, New York, NY, at the 2023 International Gynecologic Cancer Society Annual Global Meeting taking place November 5-7, 2023, in Seoul, South Korea.

GPS is an HLA-unrestricted heteroclitic immunotherapy against WT1, an antigen highly expressed in more than 85% of patients with ovarian cancer. This Phase 1/2 trial was an open-label, multicenter, multi-arm basket study examining the effects of the combination of GPS and pembrolizumab in patients with measurable advanced selected cancers. In the ovarian cancer arm of the study, the effect of the combination was investigated in patients with measurable WT1+ platinum-resistant ovarian cancer relapsed after or refractory to 1st/2nd -or later- line of therapy. Today’s presentation reported clinical efficacy and safety results as well as demographic and disease parameter data in a total of 16 evaluable patients. Historical illustrative comparisons were made between the outcomes in this study and those reported in comparable patients enrolled in the KEYNOTE-028 study, which investigated the effects of pembrolizumab monotherapy.

Study highlights include:

Patient Characteristics

17 patients enrolled; 16 safety and efficacy evaluable patients who received at least three doses of GPS and had follow-up cross-sectional imaging (CT/MRI) to determine tumor status.
Median age was 65 years (50-76).
Median number of prior lines of systemic therapy was two, while 23.5% of enrolled patients (4/17) had received 3-5 prior lines of therapy.
Efficacy

Median Overall Survival (OS) was 18.4 months, compared to historical values in comparable patients of 11-14 months with standard of care chemotherapy and 13.8 months with pembrolizumab monotherapy as shown in the KEYNOTE-028 study.
Median Progression-Free Survival (PFS) was 2.9 months, compared to eight weeks with pembrolizumab monotherapy as shown in the KEYNOTE-028 study.
Actuarial OS rates at 6, 12, and 18 months were 88%, 68%, and 57%, respectively.
43.8% (7/16) of patients achieved stable disease (SD); median duration of SD in these patients was 14.4 months.
Disease control rate (DCR), which is the sum of overall response rate (ORR) and rate of SD, was 50.1% (8/16 patients) at a median follow-up of 14.4 months; DCR for pembrolizumab alone in KEYNOTE-028 was 37.2%.
ORR was 6.3%.
An exploratory analysis of patients harboring tumors with detectable PD-L1 expression, i.e., those with a Combined Positive Score (CPS) >1, suggested the potential correlation between PD-L1 expression as quantified by the CPS in primary tumor samples and median PFS or median OS using two distinct cut-offs (CPS<1 vs CPS≥1 and CPS<10 vs CPS≥10). Reported data showed that:
All patients with CPS<1 progressed vs 36.4% of those with CPS≥1
Patients with CPS<1 had a median PFS of 1.9 months vs 3.8 months in those with CPS≥1
Patients with CPS<1 had a median OS of 3.2 months vs 18.4 months in those with CPS≥1
Safety

Treatment-related adverse events (TRAEs) were mostly grade 1-2 and occurred in about 80% of patients receiving the GPS + pembrolizumab combination.
Five patients reported 11 serious adverse events (SAEs). One SAE, grade 3 pneumonitis, was considered directly related to pembrolizumab.
The remaining 10 SAEs were reported by four patients and all unrelated or unlikely to be related to study drug.
No dose-limiting toxicities (DLT) or grade 5 events were reported.
Immune Response Profiles

WT1-specific T-cell (CD8 and CD4) immune response (IR) data showed a positive trend over time post-baseline with highest consistency and potential biomarkers for consistency being IFNγ and MIP1β.
GPS in combination with pembrolizumab was strongly immunogenic, as evidenced by the positive T-cell responses seen post-vaccination.
42.8% of patients (6/14) achieved CD8 T-cell immune response.
85.7% of patients (12/14) achieved CD4 T-cell immune response.
A correlation between WT1 specific T-cell immune responses (CD8 or CD4) and PFS was observed in a subset of analyzed patients with 41% longer PFS in patients with recorded immune response vs without (p=0.025).
"We are excited to share positive, final results from the Phase 1/2 study of GPS in combination with pembrolizumab at this year’s IGCS meeting in a highly challenging patient population of women with measurable tumor in advanced platinum resistant ovarian cancer receiving second and later lines of salvage therapy," said Dragan Cicic, MD, Senior Vice President, Clinical Development of SELLAS. "The combination shows clinical benefit in advanced ovarian cancer patients, achieving long-term disease stability and, notably, a median overall survival that exceeded 18 months, a benchmark for novel therapies, while a good safety profile was observed. The findings of 50% disease control rate and numerically superior overall survival over standard-of-care systemic therapy were consistent with the mechanism of action of GPS as a non-HLA-restricted vaccine which could be rendered more active against macroscopic metastases when aided by checkpoint blockade-induced amelioration of an immunologically adverse tumor microenvironment. Moreover, the correlation between the immune response and prolonged PFS underscores the transformative potential of GPS immunotherapy. The results strengthen our belief in GPS’s role alongside checkpoint inhibitors for WT1+ ovarian cancer and other WT1-expressing tumors, which warrant more in-depth investigation in future clinical studies in patients with measurable metastatic WT1+ malignancies, in the context of further advancing GPS’ clinical development," concluded Dr. Cicic.

The multicenter study was sponsored by SELLAS and conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Rahway, N.J., USA (known as MSD outside the United States and Canada). Based on data in this e-poster presentation, SELLAS is planning the submission of a full-length manuscript to a peer-reviewed journal during the first half of 2024.

About Ovarian Cancer

Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women in the United States. Over 22,000 cases are diagnosed annually, and there are an estimated 15,500 deaths per year. Most patients have widespread disease at presentation. The 5-year survival for advanced-stage disease remains less than 30 percent. Combining GPS with the checkpoint inhibitor pembrolizumab, which beneficially and profoundly alters the tumor microenvironment (TME) is hypothesized to increase the proportion of patients who develop an immune response against their cancer and potentially improve their clinical outcome over checkpoint inhibitors monotherapy, without the burden of additional toxicities in macroscopically measurable malignancies.

On November 6, 2023 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported that Dean Schorno, the company’s chief financial officer, will present a company overview at the Jefferies 2023 London Healthcare Conference on Tuesday, November 14, 2023 at 3:30 p.m. GMT (10:30 a.m. EST) (Press release, Rigel, NOV 6, 2023, View Source [SID1234637047]).

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To access the live webcast or archived recording, visit the Investor Relations section of the company’s website at www.rigel.com. Please connect to Rigel’s website prior to the start of the live webcast to allow for any software downloads.

On November 6, 2023 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for RAS-addicted cancers, reported its financial results for the quarter ended September 30, 2023, and provided an update on corporate progress (Press release, Revolution Medicines, NOV 6, 2023, View Source [SID1234637046]).

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Recent Highlights

RMC-6236: Revolution Medicines presented promising anti-tumor activity data for RMC-6236, a RASMULTI(ON) Inhibitor, in patients with non-small cell lung cancer (NSCLC) or pancreatic ductal adenocarcinoma (PDAC) harboring KRASG12X mutations. The data demonstrated that treatment with RMC-6236 led to meaningful clinical responses at dose levels that were generally well tolerated. The results also provided clinical validation that RMC-6236 as a RASMULTI(ON) Inhibitor can drive objective responses in patients with tumors carrying multiple common KRAS mutations, including G12D, G12V and G12R. These data support the company’s decision to advance RMC-6236 into late-stage clinical development.

RMC-6291: The company presented encouraging anti-tumor activity data for its mutant-selective RASG12C(ON) Inhibitor, RMC-6291, in patients with advanced solid tumors harboring KRASG12C mutations, including NSCLC and colorectal cancer (CRC). The data provided preliminary evidence of anti-tumor activity by treatment with RMC-6291 that was generally well tolerated across dose levels and included preliminary evidence of mechanistic and clinical differentiation from KRASG12C(OFF) inhibitors as indicated by clinical responses in NSCLC patients previously treated with a KRASG12C(OFF) inhibitor and in KRASG12C(OFF) inhibitor naïve CRC patients.

EQRx Acquisition: Last week, Revolution Medicines announced that Institutional Shareholder Services Inc. and Glass Lewis & Co. recommended Revolution Medicines stockholders vote "FOR" the issuance of Revolution Medicines shares in the previously announced all-stock acquisition of EQRx, Inc. at the special meeting of stockholders scheduled for 11:00 a.m. Eastern Time on November 8, 2023. The transaction is expected to close shortly following the stockholder vote, subject to satisfaction of customary closing conditions, including approval by both Revolution Medicines’ and EQRx’s stockholders. Each share of common stock of EQRx issued and outstanding immediately prior to the merger will be converted into the right to receive 0.1112 shares of common stock of Revolution Medicines. If the transaction is completed, Revolution Medicines expects to issue approximately 55 million shares of its common stock in connection with the merger (excluding assumed warrants and earn-out shares). The company estimates that the acquisition will add approximately $1.1 billion in net cash proceeds, after estimated post-closing EQRx wind-down and transition costs, or approximately $20 per share of common stock to be issued with the merger.
"Collectively, the clinical data presented on RMC-6236 and RMC-6291 demonstrate that these two investigational drugs have significant anti-tumor activity across dose levels that have been generally well tolerated in patients with common cancers harboring one of the four most common oncogenic RASG12 mutations. The overwhelmingly positive reaction our team heard from clinical investigators further validates the differentiation of our RAS(ON) Inhibitor platform and clearly supports continued investment in these compounds as monotherapy and/or in combination regimens," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "With the anticipated closing of the EQRx acquisition this month, the infusion of a sizable quantum of capital will allow Revolution Medicines to advance plans designed to fully realize the potential of our RAS(ON) inhibitor investigational drugs as we seek to fulfill our vision of revolutionizing treatment for patients living with RAS-addicted cancers."

Clinical and Development Highlights

Investigational RAS(ON) Inhibitors
RMC-6236 (RASMULTI)
RMC-6236 is an oral, RAS-selective, first-in-class RASMULTI(ON) Inhibitor designed to treat patients with cancers driven by a wide range of common RAS mutations. Initially being developed as monotherapy, planning is underway to also evaluate RMC-6236 in doublet combinations with mutant-selective RAS(ON) Inhibitors as well as other combination treatments.

The ongoing Phase 1/1b monotherapy trial (NCT05379985) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6236 in patients with advanced solid tumors harboring select KRASG12 mutations, including G12D, G12V and G12R and was recently expanded to include G13 and Q61 mutations. A maximum tolerated dose has not yet been defined and dose optimization is ongoing.
The company is planning a global, randomized Phase 3 study comparing RMC-6236 against docetaxel in patients with previously treated RAS-mutated NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. The study design will be finalized after regulatory feedback. The study is expected to start in 2024.
The company is also designing a potential global randomized Phase 3 trial comparing RMC-6236 against a physician’s choice of chemotherapy regimens in patients with previously treated RAS-mutated PDAC. Future study decisions will be made after additional patient follow-up regarding durability of disease control and dose optimization and regulatory feedback. The company believes the study could potentially be initiated in 2024.
A Phase 1/1b clinical trial to evaluate the combination of RMC-6236 and RMC-6291 is currently recruiting patients. Planning is also underway for additional studies of RMC-6236 in combination with standard of care therapies, including immunotherapy and chemotherapy.
RMC-6291 (RASG12C)
RMC-6291, an oral, covalent inhibitor of RASG12C(ON) designed to treat patients with cancers driven by the KRASG12C mutant, is the first of the company’s mutant-selective RAS(ON) Inhibitors to enter clinical development and the first reported clinical-stage inhibitor of KRASG12C that uses a highly differentiated mechanism of action compared to first-generation KRASG12C(OFF) inhibitors. The ongoing Phase 1/1b monotherapy trial (NCT05462717) is a multicenter, open-label, dose-escalation and dose-expansion study of RMC-6291 in patients with advanced KRASG12C mutant solid tumors. A maximum tolerated dose has not yet been defined and dose optimization is ongoing.

In addition to the Phase 1/1b combination study of RMC-6291 and RMC-6236, planning is underway for studies to evaluate RMC-6291 in combination with standard of care therapies, including immunotherapy and chemotherapy.
RMC-9805 (RASG12D)
RMC-9805 is an oral, selective, covalent inhibitor of RASG12D(ON), the most common driver of RAS-addicted human cancers, predominantly among patients with PDAC, NSCLC or CRC. The company believes RMC-9805 is the first oral and covalent inhibitor of RASG12D.

The Phase 1/1b trial (NCT06040541) is an ongoing multicenter, open-label, dose-escalation and dose-expansion study of RMC-9805 in patients with advanced solid tumors harboring the KRASG12D mutation. The primary objectives of the study are to evaluate safety and tolerability, and to inform the recommended Phase 2 dose and schedule for the compound.
RAS Innovation Engine
Beyond the first wave of clinical-stage RAS(ON) Inhibitors, the company continues expanding its pipeline of RAS(ON) Inhibitor candidates.

RAS(ON) Inhibitor development candidates include RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C).
The company continues drug discovery efforts in RAS(ON) Inhibitor pipeline expansion programs focused on RAS mutation hotspots including G12R, G13D and other important targets.
Third Quarter 2023 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $813.2 million as of September 30, 2023, compared to $644.9 million as of December 31, 2022. The increase was primarily attributable to the company’s public equity offering in March 2023.

Revenue: Total revenue was zero for the quarter ended September 30, 2023, compared to $3.4 million for the quarter ended September 30, 2022.

R&D Expenses: Research and development expenses were $107.7 million for the quarter ended September 30, 2023, compared to $69.5 million for the quarter ended September 30, 2022. The increase was primarily due to an increase in clinical trial and clinical supply manufacturing expenses for RMC-6236 and RMC-6291, research expenses associated with the company’s pre-clinical portfolio, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation.

G&A Expenses: General and administrative expenses were $15.5 million for the quarter ended September 30, 2023, compared to $10.4 million for the quarter ended September 30, 2022. The increase was primarily due to an increase in stock-based compensation and an increase in personnel-related expenses related to additional headcount.

Net Loss: Net loss was $108.4 for the quarter ended September 30, 2023, compared to net loss of $73.3 million for the quarter ended September 30, 2022.

2023 Financial Guidance
Revolution Medicines is updating its projected full year 2023 GAAP net loss to be between $385 and $415 million, which includes estimated non-cash stock-based compensation expense of $45 million and $50 million. Based on the company’s current operating plan, the company projects current cash, cash equivalents and investments can fund planned operations into 2025. The Company’s financial guidance excludes the financial impact of the proposed EQRx transaction.

Webcast
Revolution Medicines will host a webcast this afternoon, November 6, 2023, at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time). To listen to the live webcast, or access the archived webcast, please visit: View Source Following the live webcast, a replay will be available on the company’s website for at least 14 days.

On November 6, 2023 Protalix BioTherapeutics, Inc. (NYSE American: PLX), a biopharmaceutical company focused on the development, production and commercialization of recombinant therapeutic proteins produced by its proprietary ProCellEx plant cell-based protein expression system, reported financial results for the third quarter ended September 30, 2023 and provided a business update on recent regulatory, clinical and corporate developments (Press release, Protalix, NOV 6, 2023, View Source [SID1234637045]).

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"We continued our efforts this quarter towards turning Protalix into a fully-sustainable biopharmaceutical company with a growing pipeline of differentiated proprietary assets. With the approval of Elfabrio by the U.S. FDA and the European Medicines Agency earlier this year, we are pleased to see our commercial partner Chiesi Global Rare Diseases hit the ground, both in the United States and the European Union. Additionally, Chiesi is continuing to position Elfabrio for future growth with additional approvals worldwide," said Dror Bashan, Protalix’s President and Chief Executive Officer. "Our strong balance sheet coupled with our growing revenue stream allows us to focus on the continued development of our growing pipeline of assets, including PRX-115, our recombinant PEGylated uricase in development for the potential treatment of severe gout. We are continuing to enroll patients in our Phase I clinical trial evaluating the safety, pharmacokinetics, pharmacodynamics and immunogenicity of PRX-115, and look forward to continuing to progress this product candidate forward, Mr. Bashan continued. "We are proud of our achievements and look forward to an exciting future as a company with a proven platform and two approved drugs, a rich pipeline of product candidates in lucrative markets, a world-class team of dedicated employees, strong financial support with a solid balance sheet and an increasing stream of revenues."

2023 Third Quarter and Recent Business Highlights

Regulatory Advancements

The Company, together with its development and commercialization partner, Chiesi Global Rare Diseases (Chiesi), a business unit of the Chiesi Group, continued to attain marketing authorizations around the world for Elfabrio (pegunigalsidase alfa) for the treatment of adult patients with Fabry disease. Elfabrio, a PEGylated enzyme replacement therapy (ERT), is a recombinant human α-Galactosidase-A enzyme expressed in plant-cell culture that is designed to provide a long half-life.

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On August 15, 2023, Chiesi announced that the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for Elfabrio in Great Britain for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease.

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On September 11, 2023, Swissmedic, the national authorization and supervisory authority for drugs and medical products in Switzerland, announced the approval of Elfabrio in Switzerland for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease.

Clinical Developments

The Company continued to advance its First in Human (FIH) phase I clinical trial of PRX–115, a recombinant PEGylated uricase product candidate under development as a potential treatment for severe gout. To date, 32 patients have been dosed in the trial. The FIH trial is a double-blind, placebo-controlled, single ascending dose study designed to evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of PRX-115

in up to 56 patients with elevated uric acid levels (>6.0 mg/dL) and no previous exposure to PEGylated uricase. The study is being conducted at New Zealand Clinical Research (NZCR) under the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) and the Health and Disability Ethics Committee (HDEC) guidelines. We expect to announce top-line results from this study in mid-2024.

Corporate Developments

On September 14, 2023, Eliot Richard Forster, Ph.D. joined the Company’s Board of Directors as its Chairman, replacing former Chairman Zeev Bronfeld, who retired for personal reasons. In addition to his role as Chairman, Dr. Forster is serving as an independent director on the Company’s Nominating Committee.

Third Quarter 2023 Financial Highlights

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The Company recorded revenues from selling goods of $10.2 million during the three months ended September 30, 2023, an increase of $1.4 million, or 16%, compared to revenues of $8.8 million for the three months ended September 30, 2022. The increase resulted primarily from an increase of $3.0 million in sales to Chiesi, following the approvals by the FDA and the EMA of Elfabrio, and of $0.6 million in sales to Brazil, partially offset by a $2.2 million decrease in sales to Pfizer.

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The Company recorded revenues from license and R&D services of $0.2 million for the three months ended September 30, 2023, a decrease of $5.2 million, or 96%, compared to revenues of $5.4 million for the three months ended September 30, 2022. Revenues from license and R&D services are comprised primarily of revenues we recognized in connection with the Chiesi Agreements. As of March 1, 2023, sponsorship of the extension studies was transferred to Chiesi, and Chiesi is now administering all open label extension studies.

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Cost of goods sold was $4.9 million for the three months ended September 30, 2023, a decrease of $2.2 million, or 31%, from cost of goods sold of $7.1 million for the three months ended September 30, 2022. The decrease in cost of goods sold was primarily the result of the decrease in sales to Pfizer, partially offset by an increase in sales of Elfabrio to Chiesi and of Elelyso to Brazil.

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For the three months ended September 30, 2023, the Company’s total research and development expenses were approximately $3.7 million comprised of approximately $1.0 million of subcontractor-related expenses, approximately $1.9 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.6 million of other expenses. For the three months ended September 30, 2022, our total research and development expenses were approximately $7.4 million comprised of approximately $4.9 million in subcontractor-related expenses, approximately $1.7 million of salary and related expenses, approximately $0.2 million of materials-related expenses and approximately $0.6 million of other expenses. Total decrease in research and developments expenses was $3.7 million, or 50%, compared to the three months ended September 30, 2022. The decrease in research and development expenses primarily resulted from the completion of our Fabry clinical program and the regulatory processes related to the Biologics License Application (BLA) and Marketing Authorization Application (MAA) review of Elfabrio by the applicable regulatory agencies.

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Selling, general and administrative expenses were $3.7 million for the three months ended September 30, 2023, an increase of $0.9 million, or 32%, compared to $2.8 million for the three months ended September 30, 2022. The increase resulted primarily from an increase of approximately $0.6 million in salary and related expenses due to one-time cash bonuses and an increase in share-based compensation.

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Financial income, net was $0.2 million for the three months ended September 30, 2023, compared to financial expenses, net of $0.4 million for the three months ended September 30, 2022. The change resulted primarily from an increase of $0.3 million in interest income.

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In the three months ended September 30, 2023, the Company recorded income taxes of approximately $0.1 million which were primarily the result of the provision for current taxes in respect of Section 174 of the U.S. Tax Cuts and Jobs Act, which was enacted in December 2017.

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Cash, cash equivalents and short term bank deposits were approximately $41.0 million at September 30, 2023.

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Net loss for the three months ended September 30, 2023 was approximately $1.9 million, or $0.03 per share, basic, and $0.04 per share, diluted, compared to a net loss of $3.6 million, or $0.07 per share, basic and diluted, for the same period in 2022.

Conference Call and Webcast Information
The Company will host a conference call today, November 6, 2023, at 8:30 a.m. EST, to review the regulatory, clinical and corporate developments, which will also be available by webcast. To participate in the conference call, please dial the following numbers prior to the start of the call: