On November 8, 2023 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, reported financial results for the third quarter of 2023, and associated Company developments (Press release, Supernus, NOV 8, 2023, View Source [SID1234637274]).

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"Our third-quarter performance underscores the strength of our growth products, with combined Qelbree and GOCOVRI net product sales increasing 52% in the third quarter of 2023 compared to the same period last year," said Jack Khattar, President and CEO of Supernus. "In addition to our strong commercial execution, during our R&D Day in October 2023, we highlighted our pipeline of first-in-class differentiated CNS product candidates that have the potential to bolster future growth."

Qelbree Update

Total IQVIA prescriptions were 163,344 in the third quarter of 2023, an increase of 73% compared to the same period last year and 12% compared to the second quarter of 2023.
Qelbree continues to expand its base of prescribers, with approximately 24,189 prescribers in the third quarter of 2023, up from 21,291 prescribers in the second quarter of 2023.
The Company presented new data at Psych Congress 2023 in September showing improved efficacy in children ages 6 years and older with attention-deficit hyperactivity disorder (ADHD) when Qelbree is administered with stimulants, as well as in adults with ADHD who undergo long-term treatment with Qelbree.
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(1) Adjusted Operating Earnings is a non-GAAP measure and is calculated as Operating Earnings (Loss) (GAAP) plus amortization of intangible assets, share-based compensation, contingent consideration expense (gain) and depreciation. A reconciliation of the full year 2023 financial guidance for Operating Loss (GAAP) to Adjusted Operating Earnings (non-GAAP) is included under the heading "Full Year 2023 Financial Guidance – GAAP to Non-GAAP Adjustments."
(2) Total revenues, excluding Trokendi XR net product sales is a non-GAAP measure and is calculated as total revenues (GAAP) less net product sales of Trokendi XR (GAAP). A reconciliation of this measure to Total revenues (GAAP) is included under the heading "Reconciliation of GAAP Total revenues to Non-GAAP Total revenues excluding Trokendi XR net product sales."

Product Pipeline Update

The Company hosted a successful Research & Development (R&D) Day in October 2023 highlighting clinical and R&D progress and its emerging pipeline of novel CNS product candidates. During the R&D Day the Company provided a product pipeline update as set forth below:

SPN-830 (apomorphine infusion device) for treatment of PD

In November 2023, the FDA accepted the resubmission of the New Drug Application (NDA) for SPN-830 for continuous treatment of motor fluctuations ("off" episodes) in Parkinson’s disease (PD). The resubmission is now considered filed, with a user fee goal date (PDUFA date) of April 5, 2024.
SPN-820 – Novel first-in-class molecule that increases mTORC1 mediated synaptic function for depression

The Phase IIb multi-center randomized double-blind placebo-controlled parallel design study of SPN-820 in adults with treatment-resistant depression is ongoing. The study will examine the efficacy and safety of SPN-820 over a course of five weeks of treatment in approximately 268 patients in up to 50 clinical sites. The primary outcome measure is the change from baseline to end of treatment period on the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score. Topline data from the Phase IIb trial is expected in 2025.
The Company plans to initiate a Phase II open-label study in approximately 40 subjects with major depressive disorder (MDD) before year-end 2023. The primary objective of the study is to assess efficacy in MDD, as well as onset of efficacy.
SPN-817 – Novel first-in-class highly selective AChE inhibitor for epilepsy

An open-label Phase IIa clinical study of SPN-817 for treatment-resistant seizures is ongoing. The study is examining the safety and tolerability of SPN-817 as adjunctive therapy in adult patients with treatment-resistant seizures, as well as assessing efficacy. The Company expects topline results from the Phase IIa study in the first half of 2024.
The Company expects to initiate a Phase IIb randomized, double-blind, placebo-controlled study in approximately 436 patients with treatment-resistant focal seizures in the first half of 2024. The primary endpoint is change from baseline in focal seizure frequency per 28 days. Topline results from the Phase IIb study are expected in 2026.
SPN-443 – Novel stimulant for ADHD/CNS

The Company is planning in 2024 to initiate a Phase I single dose study in approximately 24 healthy adults following submission of an Investigational New Drug (IND) application. The primary objective of the study is to assess safety and tolerability.
Financial Highlights

Total revenues (GAAP and non-GAAP)

For the three months ended September 30, 2023, total revenues and total net product sales (GAAP) were $153.9 million and $149.0 million, respectively, compared to total revenues and total net product sales of $177.4 million and $172.7 million for the same period in 2022. For the nine months ended September 30, 2023, total revenues and total net product sales were $443.2 million and $417.9 million, respectively, compared to total revenues and total net product sales of $499.9 million and $485.6 million for the same period in 2022. The decrease in net product sales in both periods was primarily due to the decline in net product sales of Trokendi XR. This decline in net product sales of Trokendi XR was partially offset by an increase in net product sales of Qelbree, GOCOVRI and APOKYN for the three months ended September 30, 2023, and an increase in net product sales of Qelbree and GOCOVRI for the nine months ended September 30, 2023.

Total revenues excluding Trokendi XR net product sales (non-GAAP) for the three and nine months ended September 30, 2023, increased 24% and 25%, respectively, compared to the same periods in 2022.

The following table provides information regarding total revenues during the three and nine months ended September 30, 2023 and 2022 (unaudited, dollars in millions):

Three Months Ended
September 30, Nine Months Ended
September 30,
2023 2022 Change % 2023 2022 Change %
Total net product sales $ 149.0 $ 172.7 (14 )% $ 417.9 $ 485.6 (14 )%
Royalty revenues(1) 4.9 4.7 4 % 25.3 14.3 77 %
Total revenues (GAAP) $ 153.9 $ 177.4 (13 )% $ 443.2 $ 499.9 (11 )%
Total revenues excluding Trokendi XR net product sales (non-GAAP) $ 133.3 $ 107.8 24 % $ 368.5 $ 295.9 25 %
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(1) Royalty revenues include royalties on generic Trokendi XR, other licensed products and intellectual property.

The following table provides information regarding total net product sales during the three and nine months ended September 30, 2023 and 2022 (unaudited, dollars in millions):

Three Months Ended
September 30, Nine Months Ended
September 30,
2023 2022 Change % 2023 2022 Change %
Net product sales
Qelbree $ 37.1 $ 18.3 103 % $ 93.8 $ 37.7 149 %
GOCOVRI 32.9 27.9 18 % 87.7 75.2 17 %
Oxtellar XR 29.6 30.5 (3 )% 82.4 88.0 (6 )%
Trokendi XR 20.6 69.6 (70 )% 74.7 204.0 (63 )%
APOKYN 21.5 18.3 17 % 56.3 57.2 (2 )%
Other(1) 7.3 8.1 (10 )% 23.0 23.5 (2 )%
Total net product sales $ 149.0 $ 172.7 (14 )% $ 417.9 $ 485.6 (14 )%
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(1) Includes net product sales of MYOBLOC, XADAGO and Osmolex ER.

Operating earnings (loss) (GAAP and non-GAAP)

For the three months ended September 30, 2023, operating earnings (GAAP) was $8.1 million, compared to operating loss (GAAP) of ($1.5) million for the same period in 2022. For the nine months ended September 30, 2023, operating loss (GAAP) was ($4.3) million, compared to operating earnings (GAAP) of $11.8 million for the same period in 2022. The increase in operating earnings (GAAP) in the third quarter of 2023 was due primarily to lower selling and marketing expenses compared to the third quarter of 2022 due to the launch of Qelbree to the adult population and the Qelbree direct-to-consumer campaign, which substantially occurred in the third quarter of 2022. The operating loss (GAAP) in the nine months ended September 30, 2023 was primarily due to a decrease in net product sales of Trokendi XR, partially offset by growth in net product sales of Qelbree and GOCOVRI, and a decrease in operating expenses.

For the three months ended September 30, 2023, adjusted operating earnings (non-GAAP) were $37.3 million, compared to $25.4 million for the same period in 2022. For the nine months ended September 30, 2023, adjusted operating earnings (non-GAAP) were $77.9 million, compared to $91.1 million for the same period in 2022.

Reconciliation of GAAP Operating earnings (loss) to Non-GAAP Operating earnings

An itemized reconciliation between operating earnings (loss) on a GAAP basis and operating earnings on a non-GAAP basis is as follows (unaudited, dollars in millions):

Three Months Ended
September 30, Nine Months Ended
September 30,
2023 2022 2023 2022
Operating earnings (loss) – As Reported (GAAP) $ 8.1 $ (1.5 ) $ (4.3 ) $ 11.8
Adjustments:
Amortization of intangible assets 21.2 20.6 61.3 61.9
Share-based compensation 7.9 5.0 20.3 13.3
Contingent consideration expense (gain) (0.5 ) 0.5 (1.3 ) 1.9
Depreciation 0.6 0.8 1.9 2.2
Operating earnings – As Adjusted (non-GAAP) $ 37.3 $ 25.4 $ 77.9 $ 91.1
Non-GAAP operating earnings adjusts for non-cash items including amortization of intangible assets, share-based compensation expense, change in fair value of contingent consideration, and depreciation.

Net earnings (loss) (GAAP)

For the three months ended September 30, 2023, net earnings (loss) (GAAP) and diluted earnings (loss) per share (GAAP) were ($16.0) million and ($0.29), respectively, as compared to $1.7 million and $0.03, in the same period in 2022. For the nine months ended September 30, 2023, net earnings (GAAP) and diluted earnings per share (GAAP) were $0.1 million and $0.00, respectively, as compared to $35.2 million and $0.62 in the same period in 2022.

Balance sheet

At September 30, 2023, the Company’s cash, cash equivalents, and current and long-term marketable securities were approximately $225.3 million, compared to $555.2 million as of December 31, 2022. This decrease was primarily due to repayment of the Company’s $402.5 million 0.625% Convertible Senior Notes due 2023 (2023 Notes), partially offset by cash generated from operations.

Full Year 2023 Financial Guidance (GAAP)

The Company is revising its full-year 2023 financial guidance as set forth below (dollars in millions).

Current
(as of November 8, 2023) Previous
(as of August 8, 2023)
Total revenues(1)(2) $590 – $610 $580 – $620
Combined R&D and SG&A expenses $420 – $440 $450 – $480
Operating loss(3) ($15) – ($5) ($30) – ($10)
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(1) Includes net product sales and royalty revenue, and approximately $90 million of Trokendi XR.
(2) Reflects Trokendi XR generic erosion in 2023.
(3) Includes amortization of intangible assets and contingent consideration expense (gain).

Full Year 2023 Financial Guidance – GAAP to Non-GAAP Adjustments

An itemized reconciliation between projected operating loss on a GAAP basis and projected operating earnings on a non-GAAP basis is as follows (dollars in millions):

Current
(as of November 8, 2023) Previous
(as of August 8, 2023)
Operating loss – GAAP ($15) – ($5) ($30) – ($10)
Adjustments:
Amortization of intangible assets $83 $83
Share-based compensation $25 – $29 $20 – $24
Contingent consideration $0 – $1 $0 – $1
Depreciation $2 $2
Operating earnings – non-GAAP $95 – $110 $75 – $100
Non-GAAP Financial Information

This press release contains financial measures that present financial information which do not comply with United States generally accepted accounting principles (GAAP). The non-GAAP financial measure should be considered in addition to, not as a substitute for or in isolation from, or superior to measures prepared in accordance with GAAP. Non-GAAP operating earnings adjusts for non-cash share-based compensation expense, depreciation and amortization, and accretion of contingent consideration, and for factors that are unusual, non-recurring or unpredictable, and excludes those costs, expenses, and other specified items presented in the reconciliation tables in this press release. In addition to non-GAAP operating earnings, we also present total revenues excluding net product sales of Trokendi XR which is a non-GAAP measure and is calculated as total revenues (GAAP) less net product sales of Trokendi XR (GAAP). With the loss of exclusivity due to generic entrants, we do not expect net product sales of Trokendi XR to constitute a significant part of our revenue in the future. We believe that the use of non-GAAP financial measures provides useful supplemental information to management, investors, analysts and others regarding the Company’s revenue and results of operations and assist management, investors, analysts, and others in understanding and evaluating our revenue growth and the performance of the business.

There are limitations associated with the use of non-GAAP financial measures and therefore comparability may be limited. These limitations include: non-GAAP financial measures that may not be entirely comparable to similarly titled measures used by other companies; these may not reflect all items of income and expense, as applicable, that affect our operations; there may be potential differences among calculation methodologies; these may differ from the non-GAAP information used by other companies, including peer companies. We mitigate these limitations by reconciling the non-GAAP financial measure to the most comparable GAAP financial measure. Investors are encouraged to review the reconciliation. The Company’s 2023 financial guidance is also being provided on both a reported and a non-GAAP basis.

Reconciliation of GAAP Total revenues to Non-GAAP Total revenues excluding Trokendi XR net product sales

An itemized reconciliation between total revenues on a GAAP basis and Total revenues excluding Trokendi XR net product sales, a non-GAAP measure, is as follows (unaudited, dollars in millions):

Three Months Ended
September 30, Nine Months Ended
September 30,
2023 2022 Change % 2023 2022 Change %
Total revenues (GAAP)(1) $153.9 $177.4 (13 )% $443.2 $499.9 (11 )%
Less: Trokendi XR net product sales 20.6 69.6 (70 )% 74.7 204.0 (63 )%
Total revenues excluding Trokendi XR net product sales (Non-GAAP) $133.3 $107.8 24 % $368.5 $295.9 25 %
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(1) Includes net product sales and royalty revenue.

Conference Call Details

Supernus will host a conference call and webcast today, November 8, 2023, at 4:30 p.m. Eastern Time to discuss these results. A live webcast will be available in the Events & Presentations section of the Company’s Investor Relations website www.supernus.com/investors.

Participants may also pre-register any time before the call here. Once registration is completed, participants will be provided a dial-in number with a personalized conference code to access the call. Please dial 15 minutes prior to the start time.

Following the live call, a replay will be available on the Company’s Investor Relations website www.supernus.com/investors. The webcast will be available on the Company’s website for 60 days following the live call.

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.