On November 8, 2023 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company developing innovative therapeutics to specifically treat metastatic breast cancers harboring ESR1 mutations, reported that a case report detailing a durable complete remission during its Phase 2 ELAINE-1 study was published in JCO Precision Oncology (JCO PO) (Press release, Sermonix Pharmaceuticals, NOV 8, 2023, View Source [SID1234637273]). The case marks the first-ever known finding of a complete clinical remission in a metastatic estrogen receptor-positive (ER+)/HER2- breast cancer patient with an ESR1 mutation after prior CDK4/6 inhibitor treatment upon participation in any single-agent hormonally based therapy trial.

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The open-access case report, "Lasofoxifene Monotherapy Induces Durable Complete Remission in a Patient with ER+, HER2- Metastatic Breast Cancer with an ESR1 Mutation," details a patient result that was reported during Sermonix’s Evaluation of Lasofoxifene in ESR1 Mutations (ELAINE-1, NCT03781063) study. The case was previously presented as a poster and brief talk at the annual Metastatic Breast Cancer Research Conference in September 2022. Topline results from the ELAINE-1 trial, including this patient, were reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022.

"To witness a study participant with advanced breast cancer achieve a durable complete remission for more than two years while taking lasofoxifene is a reminder to everyone at Sermonix why we do what we do; it drives our daily and long-term vision for this drug," said Dr. David Portman, Sermonix founder and chief executive officer. "We are excited the details of this complete responder – the only one to our knowledge achieved in the post-CDK4/6i-ESR1 mutation setting with single-agent endocrine therapy – will be shared with a broader audience through JCO Precision Oncology and we look forward to lasofoxifene’s continued clinical development during our current Phase 3 ELAINE-3 registrational study."

Mutations in the ESR1 gene have emerged as an important driver of resistance to endocrine therapies that form the backbone of treatment for patients with ER+/HER2- breast cancer.

ELAINE-1 was an open-label, randomized study that evaluated the efficacy of oral lasofoxifene versus intramuscular fulvestrant for the treatment of postmenopausal women with locally advanced or metastatic ER+/HER2- breast cancer with an ESR1 mutation and progression-free survival as the primary endpoint. ELAINE-1 demonstrated that lasofoxifene numerically prolonged median progression-free survival compared with fulvestrant (5.6 vs 3.7 months; P=0.138) in metastatic breast cancer patients with ESR1 mutations who had progressed taking a prior aromatase inhibitor (AI) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), with a favorable safety profile.

"To achieve a complete response during our ELAINE-1 study was exceedingly gratifying, bolstering our confidence in lasofoxifene’s potential to address the needs of patients with ESR1 mutations," Dr. Einav Nili Gal-Yam, M.D., Ph.D., ELAINE-1 principal investigator and head of the Breast Oncology Institute at Chaim Sheba Medical Center in Ramat Gan, Israel. "We are excited to continue investigating the drug’s potential."

Breast cancer is the most common solid tumor in women worldwide and a major cause of cancer mortality, and incidence rates in the U.S. are steadily increasing every year.1-3 Approximately 80% of all breast cancers are estrogen receptor positive (ER+)4, and evidence suggests estrogen receptor alpha (ERα, encoded by ESR1) and mutations of the receptor play a critical role in the initiation and progression of these tumors.5

JCO PO is a peer-reviewed, online-only journal publishing original research, case reports, opinions, and reviews that advance the science and practice of precision oncology and define genomics- and other biomarker-driven clinical care of patients with cancer.

To read the published case report, visit JCO PO website. To learn more about the ELAINE studies, visit ElaineStudy.com.

1Pfeiffer RM, Webb-Vargas Y, Wheeler W, et al: Proportion of U.S. Trends in Breast Cancer Incidence Attributable to Long-term Changes in Risk Factor Distributions. Cancer Epidemiol Biomarkers Prev 27:1214-1222, 2018.
2Siegel RL, Miller KD, Fuchs HE, et al: Cancer Statistics, 2021. CA Cancer J Clin 71:7-33, 2021.
3Sung H, Ferlay J, Siegel RL, et al: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209-249, 2021.
4Hwang KT, Kim J, Jung J, et al: Impact of Breast Cancer Subtypes on Prognosis of Women with Operable Invasive Breast Cancer: A Population-based Study Using SEER Database. Clin Cancer Res 25:1970-1979, 2019.
5Jeselsohn R, De Angelis C, Brown M, et al: The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer. Curr Oncol Rep 19:35, 2017.

About Lasofoxifene
Lasofoxifene is an investigational novel endocrine therapy in clinical development which has demonstrated robust target engagement as an ESR1 antagonist in the breast, particularly in the presence of ESR1 mutations. Lasofoxifene has demonstrated anti-tumor activity as monotherapy and in combination with a CDK4/6 inhibitor in Phase 2 studies and has unique tissue selectivity distinguishing it from other current and investigational endocrine therapies, with beneficial effects seen on vagina and bone in previous clinical studies. Lasofoxifene, which Sermonix licensed globally from Ligand Pharmaceuticals Inc. (NASDAQ:LGND), has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a novel targeted and tissue selective oral endocrine therapy could, if approved, play a critical role in the precision medicine treatment of advanced ER+ breast cancer.

On November 8, 2023 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on changing the possible for patients through engineered cells, reported financial results and business highlights for the third quarter 2023 (Press release, Sana Biotechnology, NOV 8, 2023, View Source [SID1234637272]).

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"We continue to execute on our plans to develop our hypoimmune technology, with the potential to deliver data from four different clinical settings in 2023 and 2024," said Steve Harr, Sana’s President and Chief Executive Officer. "We have increased confidence that this platform can prevent immune recognition of allogeneic cells, unlocking the potential for important medicines in blood cancers, B-cell-mediated autoimmune diseases, and type 1 diabetes, and we look forward to sharing data later this year and next. With our recent strategic repositioning, we expect 2024 operating cash burn to be below $200 million, enabling multiple clinical data readouts with our current balance sheet and a cash runway into 2025."

Recent Corporate Highlights

Human proof of concept data in multiple clinical settings – including oncology, autoimmune diseases, and type 1 diabetes – expected in 2023 and 2024

The ARDENT trial evaluates SC291, an ex vivo HIP-modified CD19-directed allogeneic CAR T cell therapy, in patients with B-cell malignancies. The goal of the hypoimmune platform is to overcome the immunologic rejection of allogeneic cells, which, if successful with SC291, may result in longer CAR T cell persistence and a higher rate of durable complete responses for these patients.

Enrollment in the ARDENT Phase 1 study continues, and initial clinical data are expected in 2023 and more robust data expected in 2024.

The CTA was submitted for an IST evaluating an ex vivo HIP-modified primary human pancreatic islet cell therapy in patients with type 1 diabetes patients. The goal of the study is to show that transplantation of HIP-modified pancreatic islets is safe, evades immune recognition, survives, and functions without immunosuppression.
Initial HIP proof of concept data are expected in 2023 and 2024.
Sana is developing SC451, a hypoimmune-modified stem-cell derived pancreatic islet cell therapy for patients with type 1 diabetes. Sana expects insights from the IST to inform the development of SC451.
The IND has been submitted for SC291 for the treatment of multiple B-cell-mediated autoimmune diseases, and preliminary clinical data are expected in 2024.
The IND is on track for submission in 4Q 2023 for SC262, an ex vivo HIP-modified CD22-directed allogeneic CAR T cell therapy, for the treatment of B-cell lymphomas and leukemias in patients who have failed CD19-directed CAR T therapies. Preliminary clinical data are expected in 2024.
Preclinical data are scheduled for presentation at ASH (Free ASH Whitepaper) in December regarding HIP-modified CD22-directed and GPRC5D-directed allogeneic CAR T cells and topics related to fusogen specificity, extracorporeal delivery, and applications in targeting hematopoietic stem cells.

Third Quarter 2023 Financial Results

GAAP Results

Cash Position: Cash, cash equivalents, and marketable securities as of September 30, 2023 were $268.6 million compared to $434.0 million as of December 31, 2022. The decrease of $165.4 million was primarily driven by cash used in operations of $201.6 million and cash used for the purchase of property and equipment of $6.0 million. The decrease in cash was offset by net proceeds of $27.0 million from at the market equity offerings during the nine months ended September 30, 2023. The lease for our previously planned manufacturing facility in Fremont, California (the Fremont facility) was terminated during the third quarter of 2023, and the letter of credit of $6.7 million associated with this lease was returned to Sana and is included in cash and cash equivalents as of September 30, 2023.

Research and Development Expenses: For the three and nine months ended September 30, 2023, research and development expenses, inclusive of non-cash expenses, were $65.6 million and $205.8 million, respectively, compared to $76.7 million and $222.0 million for the same periods in 2022. The decrease of $11.1 million for the three months ended September 30, 2023 compared to the same period in 2022 was primarily due to decreased laboratory and research costs associated with lower research and development headcount, personnel-related costs, and third-party manufacturing costs at contract development and manufacturing organizations (CDMOs). The decrease of $16.2 million for the nine months ended September 30, 2023 compared to the same period in 2022 was primarily due to decreased laboratory and research costs, personnel-related costs, including non-cash stock-based compensation expense, third-party manufacturing costs at CDMOs, costs to acquire technology, and costs related to the Fremont facility that are now included in general and administrative expense. These decreases were partially offset by increased clinical development costs, non-cash lease costs for Sana’s planned manufacturing facility in Bothell, Washington (the Bothell facility), and depreciation. Research and development expenses include non-cash stock-based compensation of $5.7 million and $18.4 million, respectively, for the three and nine months ended September 30, 2023, and $7.4 million and $20.6 million, for the same periods in 2022.

Research and Development Related Success Payments and Contingent Consideration: For the three and nine months ended September 30, 2023, Sana recognized gains of $82.6 million and $55.8 million, respectively, in connection with the change in the estimated fair value of the success payment liabilities and contingent consideration in aggregate, compared to gains of $6.1 million and $79.4 million for the same periods in 2022. The value of these potential liabilities may fluctuate significantly with changes in Sana’s market capitalization and stock price.
General and Administrative Expenses: General and administrative expenses for the three and nine months ended September 30, 2023, inclusive of non-cash expenses, were $19.2 million and $52.5 million, respectively, compared to $15.5 million and $48.2 million for the same periods in 2022. The increase of $3.7 million for the three months ended September 30, 2023 compared to the same period in 2022 was primarily due to a loss on termination of lease associated with the Fremont facility (Fremont lease) and an increase in patent and other legal fees. These increases were partially offset by a decrease in insurance costs. The increase of $4.3 million for the nine months ended September 30, 2023 compared to the same period in 2022 was primarily due to an increase in patent and other legal fees, a loss on termination of the Fremont lease, non-cash stock-based compensation, costs related to the Fremont facility, which were formerly in research and development expense, and consulting fees. These increases were partially offset by the write-off of construction in progress costs in 2022 for the Fremont facility, and a decrease in insurance costs.

Net Loss: Net income for the three months ended September 30, 2023 was $1.0 million, or $0.00 per share, and net loss for the nine months ended September 30, 2023 was $195.1 million, or $1.01 per share. Net loss for the three and nine months ended September 30, 2022 were $85.1 million, or $0.45 per share, and $189.0, or $1.01 per share, respectively.
Non-GAAP Measures

Non-GAAP Operating Cash Burn: Non-GAAP operating cash burn for the nine months ended September 30, 2023 was $187.2 million compared to $219.8 million for the same period in 2022. Non-GAAP operating cash burn is the decrease in cash, cash equivalents, and marketable securities, excluding cash inflows from financing activities, cash outflows from business development, costs related to the early termination of the Fremont lease, non-recurring items, and the purchase of property and equipment.

Non-GAAP General and Administrative Expenses: Non-GAAP general and administrative expenses for the three and nine months ended September 30, 2023 was $16.5 million and $49.8 million, respectively, compared to $15.5 million and $43.8 million for the same periods in 2022. Non-GAAP general and administrative expense excludes the loss on termination of the Fremont lease and the write-off of construction in progress costs incurred in connection with the Fremont facility in 2022.

Non-GAAP Net Loss: Non-GAAP net loss for the three and nine months ended September 30, 2023 was $79.0 million, or $0.41 per share, and $248.3 million, or $1.28 per share, respectively, compared to $91.2 million, or $0.48 per share, and $264.0 million, or $1.42 per share for the same periods in 2022. Non-GAAP net loss excludes non-cash expenses and gains related to the change in the estimated fair value of contingent consideration and success payment liabilities, the loss on termination of the Fremont lease, and the write-off of construction in progress costs incurred in connection with the Fremont facility in 2022.
A discussion of non-GAAP measures, including a reconciliation of GAAP and non-GAAP measures, is presented below under "Non-GAAP Financial Measures."

On November 8, 2023 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of oncolytic immunotherapies, reported updated data from a cohort of metastatic uveal melanoma patients enrolled in the open-label, multicenter, Phase 1 study of RP2 as a single agent and in combination with nivolumab (Press release, Replimune, NOV 8, 2023, View Source [SID1234637271]). The data were presented by Dr. Joseph Sacco during a Plenary Session at the 20th International Congress of the Society for Melanoma Research in Philadelphia.

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Treatment with RP2 led to an overall response rate (ORR) of 29.4 percent (5 of 17 patients; one of the responding patients was treated with RP2 monotherapy and four of the responding patients were treated with RP2 combined with nivolumab), including responses in patients with liver, lung, and bone metastases. The median duration of response (DOR) at the data cutoff was 11.47 months (range of 2.78 to 21.22 with responses ongoing). Nearly all patients (15 of 17, 88.2%) in the study had progressed on or after immunotherapy with 12 of 17 patients (70.6%) having received both prior anti-PD1 and anti-CTLA-4 therapy, including four of the responding patients. The slides are available on our website under presentations.

RP2 was generally well tolerated both as monotherapy and in combination with nivolumab with no additive adverse events observed. The most common grade 1 or 2 treatment related adverse events (TRAEs) overall in both cohorts were pyrexia, chills, fatigue, hypotension and pruritis. Six patients had grade 3 TRAEs, including two cases of hypotension. There were no grade 4 or 5 TRAEs.

"Metastatic uveal melanoma is an immunologically cold tumor type with few effective treatment options," said Joseph Sacco, MBChB, PhD, FRCP, University of Liverpool and Clatterbridge Cancer Centre, UK. "In fact, single-agent and combination immune checkpoint inhibitor therapies, including ipilimumab combined with nivolumab, exhibit low response rates in patients with this disease, with combination therapies associated with significant toxicity. The data from this study are compelling given the rate of durable responses seen combined with a favorable safety profile, including in patients who had both liver and extra-hepatic metastases, further supporting the potential of RP2 in this patient population."

Uveal melanoma is the most common form of intraocular primary malignancy and accounts for approximately 90 percent of all cases of ocular melanoma and up to 5 percent of all melanomas. Approximately 50 percent of patients will develop distant metastases, with about 90 percent of such patients manifesting liver metastases. Once the disease metastasizes, median overall survival is less than one year.

"These data from the trial cohort evaluating RP2 as monotherapy and in combination with nivolumab in metastatic uveal melanoma are highly promising," said Robert Coffin, President and Chief Research & Development Officer at Replimune. "We are currently assessing the potential registrational path forward for RP2 in advanced uveal melanoma now that the Phase 1 development of RP2 in this disease is nearly complete. Metastatic uveal melanoma is a disease with significant unmet medical need where treatments remain limited, and no current standard of care options provide the potential for long term survival, other than in a minority of patients."

About RP2
RP2 is a derivative of RP1, Replimune’s lead product candidate that is based on a proprietary new strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP-R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity.

On November 8, 2023 Nuvectis Pharma, Inc (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, reported its financial results for the third quarter 2023 and provided an update on recent business progress (Press release, Nuvectis Pharma, NOV 8, 2023, View Source [SID1234637270]).

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Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis, commented, "In the third quarter we continued to advance the development programs of NXP800 and NXP900. The NXP800 Phase 1b study in platinum resistant, ARID1a-mutated ovarian carcinoma, a disease of unmet medical need, continues and we expect to report preliminary data from the study in 1Q 2024. In addition, the Food and Drug Administration ("FDA") granted NXP800 Orphan Drug Designation for the treatment of Cholangiocarcinoma, another deadly disease of unmet need." Mr. Bentsur continued, "For NXP900, we initiated the dose escalation part of our Phase 1 study in patients with advanced solid tumors and published additional preclinical data highlighting the potential of NXP900 to treat tumors of squamous cell origin, including those with HIPPO pathway mutations." Mr. Bentsur concluded, "Finally, we continue to be judicious with our financial resources and ended the quarter with approximately $22.1 million, which we expect will allow us to meet important milestones for both clinical programs and provide working capital into 1H 2025."

Third Quarter 2023 Financial Results

Cash, cash equivalents, and short-term investments were $22.1 million as of September 30, 2023, compared to $20.0 million as of December 31, 2022. The increase of $2.1 million was primarily a result of the exercise of warrants from the July 2022 private investment in public equity ("PIPE") transaction.

The Company’s net loss was $5.9 million for the three months ended September 30, 2023, compared to $5.9 million for the three months ended September 30, 2022. The net loss included $1.1 million in non-cash expenses related to stock-based compensation, $0.8 million in one-time development costs in connection with NXP800, and $0.5 million in a one-time milestone payment associated with NXP900.

Research and development expenses were $4.5 million for the three months ended September 30, 2023, compared to $4.5 million for the three months ended September 30, 2022.

General and administrative expenses were $1.7 million for the three months ended September 30, 2023, compared to $1.4 million for the three months ended September 30, 2022.

On November 8, 2023 Neurocrine Biosciences, Inc. (Nasdaq: NBIX) reported that it will present at the Jefferies London Healthcare Conference on Tuesday November 14, 2023 at 3:00 p.m. Greenwich Mean Time (10:00 a.m. Eastern Time) in London (Press release, Neurocrine Biosciences, NOV 8, 2023, View Source [SID1234637269]). Kevin Gorman, Chief Executive Officer, and additional members of Neurocrine management will present at the conference.

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The live presentation will be webcast and may be accessed on Neurocrine Biosciences’ website under Investors at www.neurocrine.com. A replay of the webcast will be available on the website approximately one hour after the conclusion of the event and will be archived for approximately one month.