On August 3, 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 second quarter 2023 (Press release, Sana Biotechnology, AUG 3, 2023, View Source [SID1234633775]).

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"We continue to execute on our plans to deliver clinical data using Sana’s hypoimmune (HIP) technology in two studies later in 2023, providing insight into how the promising preclinical HIP data translate into people," said Steve Harr, Sana’s President and Chief Executive Officer. "If the HIP technology is effective in preventing rejection of allogeneic cells, we believe it can rapidly translate into important therapeutics for various blood cancers, B-cell mediated autoimmune diseases, and type 1 diabetes. We are on track to advance our emerging clinical pipeline and file multiple additional INDs this year, and we have the balance sheet to enable multiple clinical data readouts from our pipeline."

Recent Corporate Highlights

Opportunity for clinical proof of concept for two different first-in-human studies, each with the potential for initial clinical data this year

The ARDENT trial evaluates SC291, an ex vivo hypoimmune-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 continued.
SC291 has the potential to serve as clinical proof-of-platform for other hypoimmune-modified CAR T cell candidates using clinically-validated or commercially-approved CAR constructs in development at Sana for hematological malignancies, such as SC262 (CD22) and SC255 (BCMA). Sana’s goal is to file an IND for SC262 later this year and for SC255 in 2024.
Sana is developing SC451, a hypoimmune-modified stem-cell derived islet cell therapy for patients with type 1 diabetes. SC451, which is engineered with Sana’s hypoimmune technology, has the potential to replace missing islet cells without immunosuppression in persons with type 1 diabetes by evading allogeneic and autoimmune responses.
Sana expects initial data later this year from an investigator-sponsored trial transplanting hypoimmune-modified primary human islet cells into type 1 diabetes patients. The goal of the study is to show safety, cell survival, immune evasion, and C-peptide production without the need for immunosuppression.
Sana’s goal is to file an IND for SC451 in 2024.
Published preclinical data in Nature Communications describing immune evasion, persistence, and durable anti-tumor activity of Sana’s hypoimmune-modified CD19-directed CAR T cells

Sana developed hypoimmune-modified CD19 targeted allogeneic CAR T cells and compared them to unmodified CD19-targeted allogeneic CAR T cells in a murine leukemia model with a humanized immune system.
Although both hypoimmune-modified and unmodified CAR T cells showed robust early tumor killing, cell durability was much greater in humanized mice treated with hypoimmune-modified cells. Hypoimmune-modified allogeneic CAR T cells persisted and removed all evidence of tumor for the duration of the study. Hypoimmune-modified CAR T cells also cleared all evidence of tumor after re-injection with cancer cells 90 days into the study. In contrast and consistent with the experience in patients to date, unmodified allogeneic CAR T cells showed greatly reduced persistence and a high rate of tumor recurrence in this model.
These studies provide additional insight for SC291 and the allogeneic hypoimmune CAR T platform more broadly, including SC262 and SC255.
Published preclinical data in Science Translational Medicine demonstrating that Sana’s hypoimmune-modified pseudo-islets control type 1 diabetes

Sana developed hypoimmune-modified human islet cells, which cluster into effective endocrine organoids termed "pseudo islets" (p-islets) and studied these p-islets in multiple preclinical models.
Preclinical data showed that p-islets survive, persist, escape allogeneic rejection, and normalize blood glucose in diabetic models with humanized immune systems.
Two different murine models showed that the hypoimmune-modified cells can evade autoimmune rejection and normalize blood glucose. First, these cells were studied in the standard model for autoimmunity in diabetes. Second, Sana created a humanized mouse model with immune cells from a diabetic person and transplanted pancreatic islet cells derived from the diabetic person’s stem cells. In both cases, unmodified pancreatic islet cells were rapidly cleared by the immune system. In contrast, hypoimmune-modified pancreatic islet cells survived, persisted, and provided sustained blood glucose control in both models.
These studies provide additional insight for SC451 in persons with type 1 diabetes.
Published preclinical data in Nature Biotechnology demonstrating that Sana’s hypoimmune-modified cells survive allogeneic transplant across several species, including non-human primates (NHPs) with normal immune systems, and remain fully functional

Sana developed hypoimmune-modified NHP induced pluripotent stem cells (iPSCs) and transplanted them into immunocompetent NHPs. Results were compared to transplantation of unmodified iPSCs into immunocompetent NHPs.
Data showed that hypoimmune-modified iPSCs survived for the duration of the study (16 weeks), while unmodified iPSCs disappeared within two weeks. There was an antibody and T cell response directed toward unmodified cells, but not hypoimmune-modified cells.
Hypoimmune-modified primary NHP pancreatic islet cells survived 40 weeks (duration of the study) after allogeneic transplantation into an immunocompetent NHP versus less than one week for unmodified primary islet cells.
Hypoimmune-modified iPSCs were differentiated into pancreatic islet cells. Transplantation of hypoimmune-modified iPSC-derived pancreatic cells into allogeneic diabetic mice with a humanized immune system showed immune evasion after transplantation for the duration of the studies (4 weeks) and amelioration of diabetes and normalization of blood glucose levels.
Presented multiple abstracts at several medical conferences, including AACR (Free AACR Whitepaper), ASGCT (Free ASGCT Whitepaper), and ISSCR 2023, highlighting both the hypoimmune and fusogen platforms

ISSCR:
Presented preclinical data showing that hypoimmune-modified CD19-directed CAR T cells have the potential to serve as a universal off-the-shelf therapy with long-term durability of response without immunosuppression.
Presented preclinical data showing HIP-modified primary pancreatic islet cells alleviate diabetes in humanized mice and avoid immune rejection without immunosuppression.
Presented preclinical data showing that intramuscular administration of islet cells in humanized mice does not impact cell function and viability and may serve as a preferred administration route for patients.
Presented preclinical data showing in vivo delivery of genetic payloads to human hematopoietic stem/progenitor cells.
ASGCT:
Presented preclinical data demonstrating a novel technique to detect peripheral blood CAR+ T cells.
Presented preclinical data demonstrating cell-specific transduction, CAR expression, and target cell killing, which supports the safety of in vivo administration of Sana’s novel CD8-targeted fusosomes for CAR T therapies.
Presented multiple process improvements in CD8-targeted fusosome manufacturing that enhance fusosome transduction of resting T cells in vitro and in vivo, including in vitro and in vivo tumor killing.
Presented the development of a modular approach to generate fusosomes for targeted gene delivery.
AACR:
Presented preclinical data demonstrating that hypoimmune-modified CAR T cells provide lasting tumor control in immunocompetent allogeneic humanized mice even with tumor re-challenge.
Presented preclinical data in a late-breaking poster presentation demonstrating that the increased potency of CD8-targeted fusosomes enhances CAR transgene delivery to resting primary T cells.
Presented preclinical data demonstrating the effectiveness of Sana’s fully human CD19 CAR delivered by CD8-targeted fusosomes in tumor killing assays. These fusosomes led to similar levels of tumor control as ex vivo generated CD19 CAR T cells.
Presented preclinical data demonstrating increased potency of CD8-targeted fusosomes delivering a CD19 CAR with pre-treatment of resting T cells with IL-7, rapamycin, or both. Pre-treatment with these molecules led to increased anti-tumor efficacy through increased T cell transduction and greater CAR T cell expansion.
Strengthened Research and Development leadership with the appointment of two seasoned drug developers

Appointed Doug Williams, Ph.D., as President of Research and Development. Dr. Williams has over 30 years of experience leading R&D organizations – including at Biogen, Seattle Genetics (now Seagen), Amgen, and Immunex – and over the course of his career has participated in the development of over a dozen approved drugs including multiple blockbusters.
Appointed Gary Meininger, M.D., as Chief Medical Officer. Dr. Meininger has approximately 20 years of experience in drug development. Most recently, he was at Vertex as Senior Vice President, Head of Clinical Development for Vertex Cell and Genetic Therapies and previously was at Janssen and Merck. Dr. Meininger is currently the industry representative to the FDA’s Endocrine and Metabolic Drug Advisory Committee.
Second Quarter 2023 Financial Results

GAAP Results

Cash Position: Cash, cash equivalents, and marketable securities as of June 30, 2023 were $325.9 million compared to $434.0 million as of December 31, 2022. The decrease of $108.1 million was primarily driven by cash used in operations of $138.1 million and cash used for the purchase of property and equipment of $3.7 million. The decrease in cash was offset by net proceeds of $27.0 million from at the market equity offerings during the six months ended June 30, 2023.
Research and Development Expenses: For the three and six months ended June 30, 2023, research and development expenses, inclusive of non-cash expenses, were $73.0 million and $140.2 million, respectively, compared to $72.5 million and $145.2 million for the same periods in 2022. The increase of $0.5 million for the three months ended June 30, 2023 compared to the same period in 2022 was primarily due to an increase in clinical development costs, non-cash lease costs for our planned manufacturing facility in Bothell, Washington (the Bothell facility), personnel-related costs, and depreciation expense. These increases were partially offset by a decrease in costs for laboratory supplies, third-party manufacturing costs, and costs related to the previously planned manufacturing facility in Fremont, California (the Fremont facility) that are now included in general and administrative expense. The decrease of $5.0 million for the six months ended June 30, 2023 compared to the same period in 2022 was primarily due to a decline in costs to acquire technology, laboratory supplies, third-party manufacturing, 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, personnel-related costs, non-cash lease costs for the Bothell facility, depreciation expense, and other allocated costs. Research and development expenses include non-cash stock-based compensation of $6.7 million and $12.7 million, respectively, for the three and six months ended June 30, 2023, and $7.4 million and $13.1 million, for the same periods in 2022.
Research and Development Related Success Payments and Contingent Consideration: For the three and six months ended June 30, 2023, we recognized expenses of $26.7 million and $26.8 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 $17.9 million and $73.4 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 six months ended June 30, 2023, inclusive of non-cash expenses, were $16.6 million and $33.3 million, respectively, compared to $18.3 million and $32.7 million for the same periods in 2022. The decrease of $1.7 million for the three months ended June 30, 2023 compared to the same period in 2022 was primarily due to the write-off of construction in progress costs in 2022 for the Fremont facility, partially offset by an increase in legal fees, non-cash stock-based compensation, and costs related to the Fremont facility, formerly in research and development expense. The increase of $0.6 million for the six months ended June 30, 2023 compared to the same period in 2022 was primarily due to an increase in personnel-related costs including non-cash stock-based compensation, costs related to the Fremont facility, formerly in research and development expense, and legal fees, partially offset by the write-off of construction in progress costs for the Fremont facility.
Net Loss: Net loss for the three and six months ended June 30, 2023 was $114.0 million, or $0.59 per share, and $196.1 million, or $1.02 per share, respectively, compared to $72.5 million, or $0.39 per share, and $103.9, or $0.56 per share for the same periods in 2022.
Non-GAAP Measures

Non-GAAP Operating Cash Burn: Non-GAAP operating cash burn for the six months ended June 30, 2023 was $136.5 million compared to $155.4 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, 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 six months ended June 30, 2023 was $16.6 million and $33.3 million, respectively, compared to $13.8 million and $28.3 million for the same periods in 2022. Non-GAAP general and administrative expense excludes the write-off of construction in progress costs incurred in connection with the Fremont facility.
Non-GAAP Net Loss: Non-GAAP net loss for the three and six months ended June 30, 2023 was $87.3 million, or $0.45 per share, and $169.3 million, or $0.88 per share, respectively, compared to $85.9 million, or $0.47 per share, and $172.8 million, or $0.93 per share for the same periods in 2022. Non-GAAP net loss excludes non-cash expenses related to the change in the estimated fair value of contingent consideration and success payment liabilities.
A discussion of non-GAAP measures, including a reconciliation of GAAP and non-GAAP measures, is presented below under "Non-GAAP Financial Measures."

On August 3, 2023 Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of tumor-directed oncolytic immunotherapies, reported financial results for the fiscal first quarter ended June 30, 2023 and provided a business update (Press release, Replimune, AUG 3, 2023, View Source [SID1234633774]).

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"It was a productive quarter with positive updates for RP1 in anti-PD1 failed melanoma and RP2 in uveal melanoma presented at ASCO (Free ASCO Whitepaper). The duration of responses are particularly impressive with all responding patients in the anti-PD1 failed melanoma 75 patient cohort presented late last year continuing without progression," said Philip Astley-Sparke, CEO of Replimune. "We now look forward to presenting the top-line data from our registration-directed CERPASS trial of RP1 in combination with Libtayo in cutaneous squamous cell carcinoma (CSCC) as well as sharing an initial snapshot from the full patient population in the IGNYTE clinical trial cohort of RP1 combined with Opdivo in anti-PD1 failed melanoma later in the year. Commercial preparations are progressing, and in line with our ambition of establishing a major skin cancer franchise, we are pleased to announce that we have entered a cost sharing collaboration with Incyte to conduct a clinical trial for the neoadjuvant treatment of CSCC with RP1 and the oral PD-L1 inhibitor, INCB99280."

Program Highlights & Milestones

RP1

CERPASS clinical trial of RP1 combined with Libtayo in CSCC
The trigger for the primary analysis from the registration-directed CERPASS clinical trial occurred in late June and data collection activities are nearly complete. Guidance for the top line data disclosure has been updated from Q3 to early Q4 2023 as a result of the independent review read rate tracking behind projections. Assuming positive data demonstrating overall clinical benefit, the Company plans to submit a biologics license application (BLA) for RP1 in Q1/2 2024, with the potential to combine the filings for both the CERPASS clinical trial and the IGNYTE anti-PD1 failed melanoma cohort.
Announced Clinical Trial Collaboration with Incyte to Evaluate RP1 and INCB099280 in CSCC
Under the terms of the agreement, Incyte will initiate and sponsor a clinical trial of INCB99280 (oral PD-L1 inhibitor) and RP1 in approximately 40 patients with unresectable, high risk CSCC in the neoadjuvant setting. Replimune will supply Incyte with RP1 for the study and share costs.
RP1 combined with Opdivo (nivolumab) in anti-PD1 failed non-melanoma skin cancers
Recruitment remains ongoing into the cohort of patients with anti-PD1 failed non-melanoma skin cancers, including CSCC, with a data update expected from the first 30 patients with at least six months follow up in early Q4 2023.
RP1 in solid organ transplant recipients with skin cancers
Presented initial data from the ARTACUS clinical trial of RP1 monotherapy in solid organ transplant recipients with skin cancers at the American Transplant Congress (ATC) Meeting in June. These data included 11 evaluable patients with cutaneous squamous cell carcinoma (N=10) and Merkel cell carcinoma (N=1).
The data demonstrated an overall response rate (ORR) of 27.3%, with all responders achieving confirmed complete responses (CR).
RP1 monotherapy was well tolerated, and the safety profile was similar to non-immunocompromised patients with advanced skin cancers (IGNYTE study). No immune-mediated adverse events or evidence of allograft rejection were observed.
RP1 combined with Opdivo in anti-PD1 failed melanoma
Presented updated data from the ongoing IGNYTE clinical trial at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June. These data included the first 75 patients from the anti-PD1 failed melanoma cohort combined with the 16 anti-PD1 failed melanoma patients from the prior all comers 30 patient melanoma cohort (N=91 in total).
The data demonstrated an overall response rate (ORR) of 37.4%, with clinically meaningful activity across the range of anti-PD1 failed cutaneous melanoma settings enrolled, including in patients with moderate-high tumor burden and with visceral disease.
Systemic activity was seen in both injected and un-injected lesions, with both responding with similar durability and kinetics, including in un-injected visceral disease.
RP1 continues to be generally well tolerated with safety data showing predominantly ‘on target’ flu-like Grade 1-2 side effects indicative of systemic immune activation. Grade 3 treatment related events were rarely seen in the 91-patient group, with a range of Grade 3 events in one patient each, and two Grade 3 events of fatigue. There were two Grade 4 treatment related events (elevated lipase, and cytokine release syndrome) and no treatment related Grade 5 events.
The Company remains on track to announce snapshot data for all patients (N=141) in Q4 2023 by which point all patients will have had at least 6 months follow up, prior to the per protocol primary analysis at 12 months post the last patient enrolled.
RP2 and RP3

RP2 combined with nivolumab in uveal melanoma
Presented updated data from an ongoing Phase 1b trial of RP2 at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June. To date 17 patients have been treated with RP2 as monotherapy (N=3) or in combination with nivolumab (N=14) to date, with enrollment of uveal melanoma patients into this clinical trial now being complete.
In uveal melanoma, four of the 14 evaluable patients have thus far responded to treatment (28.6%), including metastatic tumors in the liver and bone. The final three of 17 patients remain on treatment, but currently have insufficient follow-up data to determine response outcome as of the cut-off date. Three of the four responses are ongoing at 9, 12 and 21 months, including for patients with liver and bone metastases, with the fourth patient having progressed at 15 months.
The safety profile as monotherapy and in combination with nivolumab was generally well tolerated with no additive adverse events observed.
RP2 and RP3 Phase 2 program
RP2 and RP3 in combination with atezolizumab and bevacizumab in third-line colorectal cancer (CRC)
Two signal finding cohorts of 30 patients each will be enrolled in collaboration with Roche. The first cohort will enroll patients to be treated with atezolizumab combined with bevacizumab and RP2 and the second cohort with atezolizumab and bevacizumab and RP3. The Company believes that data with both RP2 and RP3 in CRC will allow the comparative efficacy of RP2 and RP3 to be evaluated in a particularly difficult to treat patient population. This clinical trial has now been initiated.

RP3 in combination with atezolizumab and bevacizumab in first (1L) and second-line (2L) hepatocellular carcinoma (HCC)
Two signal finding cohorts of 30 patients each will be enrolled in collaboration with Roche. The first cohort will enroll 1L patients treated with SOC atezolizumab combined with bevacizumab and RP3, and the second cohort will enroll patients who have progressed on 1L immunotherapy (including atezolizumab/bevacizumab), and will be treated with atezolizumab combined with bevacizumab and RP3. This clinical trial is expected to initiate this quarter.

RP3 in combination with standard of care therapy in squamous cell carcinoma of the head and neck (SCCHN)
A two-cohort clinical trial is planned, with the first cohort of 100 patients with locally advanced disease being randomized to receive either standard of care (SOC) cisplatin chemotherapy combined with radiation or RP3 combined with chemotherapy and radiation followed by adjuvant nivolumab therapy. The second, signal finding cohort, will enroll 30 patients with recurrent or metastatic SCCHN with low PDL1 levels (CPS<20) who will be treated with chemotherapy (carbopltin and paclitaxel), nivolumab and RP3. Due to the the global shortage of cisplatin and carboplatin, initiation of this study is currently on hold until sufficient supplies of these agents are available.
RP2 and RP3 Phase 1 program
Accrual in the Phase 1 program is expected to materially complete in Q3 2023. Any additional Phase 2 development programs not already announced which are driven by data from the full Phase 1 data and other opportunistic considerations are expected to be disclosed by year end.
Corporate Update

Announced the appointment of new member to Board of Directors
The Company appointed Veleka R. Peeples-Dyer, strategic enterprise leader and former Chair of the North American Food and Drug practice and Co-Chair of the Global Regulatory Group at Baker McKenzie, to the Company’s Board of Directors effective June 1, 2023. The appointment strengthens the Company’s board as it prepares for the anticipated commercialization of its leading pipeline of oncolytic immunotherapies, beginning with the potential 2024 commercial launch of RP1.
Financial Highlights

Cash Position: As of June 30, 2023, cash, cash equivalents and short-term investments were $539.1 million, as compared to $583.4 million as of March 31, 2023. The decrease was primarily related to cash utilized in operating activities in advancing the Company’s expended clinical development plans.

Based on the current operating plan, the Company believes that existing cash, cash equivalents and short-term investments, as of June 30, 2023, will enable the Company to fund operations into the second half of calendar year 2025.
R&D Expenses: Research and development expenses were $40.4 million for the first quarter ended June 30, 2023, as compared to $29.5 million for the first quarter ended June 30, 2022. This increase was primarily due to increased clinical and manufacturing expenses driven by the Company’s lead programs and increased personnel expenses. Research and development expenses included $3.3 million in stock-based compensation expenses for the first quarter ended June 30, 2023.

S,G&A Expenses: Selling, general and administrative expenses were $15.2 million for the first quarter ended June 30, 2023, as compared to $11.4 million for the first quarter ended June 30, 2022. The increase was primarily driven by personnel related costs, including sales and marketing personnel associated with pre-launch planning and build of the Company’s commercial infrastructure. Selling, general and administrative expenses included $5.5 million in stock-based compensation expenses for the first quarter ended June 30, 2023.

Net Loss: Net loss was $49.6 million for the first quarter ended June 30, 2023, as compared to a net loss of $42.3 million for the first quarter ended June 30, 2022.
About CERPASS
CERPASS is Replimune’s registration-directed randomized, global Phase 2 clinical trial to compare the effects of Libtayo (cemiplimab-rwlc) alone versus a combination of Libtayo and Replimune’s investigational oncolytic immunotherapy RP1. The clinical trial recently completed enrollment and enrolled 211 patients with locally advanced or metastatic cutaneous squamous cell carcinoma who are naïve to anti-PD-1 therapy. The clinical trial will evaluate complete response rate and overall response rate as its two independent primary efficacy endpoints as assessed by independent review, as well as secondary endpoints including duration of response, progression-free survival, and overall survival. The clinical trial is being conducted under a clinical trial collaboration agreement with Regeneron and full commercial rights retained by Replimune. Libtayo is a registered trademark of Regeneron.

About IGNYTE
IGNYTE is Replimune’s multi-cohort Phase 1/2 trial of RP1 plus nivolumab. There are 3 tumor specific cohorts currently enrolling in this clinical trial including a 125-patient cohort in anti-PD1 failed melanoma with registrational intent. This cohort was initiated after completing enrollment in a prior Phase 2 cohort in the same clinical trial of approximately 30 patients with melanoma. The additional cohorts are in non-melanoma skin cancers which includes both naïve and anti-PD1 failed CSCC, and in anti-PD1 failed microsatellite instability high, or MSI-H/dMMR tumors. This trial is being conducted under a collaboration and supply agreement with Bristol-Myers Squibb.

About RP1
RP1 is Replimune’s lead product candidate and 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.

About RP2 & RP3
RP2 and RP3 are derivatives of RP1 that express additional immune-activating proteins. RP2 expresses an anti-CTLA-4 antibody-like molecule and RP3 additionally expresses the immune co-stimulatory pathway activating proteins CD40L and 4-1BBL, but does not express GM-CSF. RP2 and RP3 are 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 August 3, 2023, Replimune Group, Inc. (the "Company") reported to have entered into a Sales Agreement (the "Sales Agreement") with Leerink Partners LLC (formerly known as SVB Securities LLC) (the "Agent"), pursuant to which the Company may sell, from time to time, at its option, up to an aggregate of $250.0 million of shares of the Company’s common stock, $0.001 par value per share (the "Shares"), through the Agent, as the Company’s sales agent (Filing, 8-K, Replimune, AUG 3, 2023, View Source [SID1234633773]).

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Any Shares to be offered and sold under the Sales Agreement will be issued and sold (i) by methods deemed to be an "at the market offering" as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended, or if authorized by the Company, in negotiated transactions or block trades, and (ii) pursuant to an automatically effective registration statement on Form S-3 filed by the Company with the Securities and Exchange Commission on August 3, 2023 for an offering of various securities, including shares of the Company’s common stock, preferred stock, debt securities, warrants and/or units for sale to the public in one or more public offerings.

Subject to the terms of the Sales Agreement, the Agent will use reasonable efforts to sell the Shares from time to time, based upon the Company’s instructions (including any price, time or size limits or other customary parameters or conditions the Company may impose). The Company cannot provide any assurances that it will issue any Shares pursuant to the Sales Agreement. The Company will pay the Agent a commission of up to 3.0% of the gross proceeds from the sale of the Shares, if any. The Company has also agreed to provide the Agent with customary indemnification rights.

Pursuant to the Sales Agreement, the parties mutually agreed to terminate that certain sales agreement, dated June 23, 2022, by and between the Company and the Agent (as amended, the "2022 Sales Agreement") with respect to the Company’s previous at-the-market offering program (the "2022 ATM Program").

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the Shares nor shall there be any sale of the Shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, which is attached hereto as Exhibit 1.1 and is incorporated by reference herein.

On August 3, 2023 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the second quarter of 2023 and provided a business update (Press release, Regeneron, AUG 3, 2023, View Source [SID1234633772]).

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"Regeneron delivered strong financial results in the second quarter of 2023 through increasingly diversified revenue streams, and we remain well-positioned for long-term growth," said Leonard S. Schleifer, M.D., Ph.D., Board Co-Chair, President and Chief Executive Officer of Regeneron. "In the past months, we have continued to advance our pipeline, in particular aflibercept 8 mg which we are progressing towards a potential FDA decision in the third quarter and for which we shared unprecedented two-year results in the pivotal PHOTON trial demonstrating durable vision gains at extended dosing intervals in patients with diabetic macular edema."

Financial Highlights

($ in millions, except per share data) Q2 2023 Q2 2022 % Change
Total revenues $ 3,158 $ 2,857 11 %
GAAP net income $ 968 $ 852 14 %
GAAP net income per share – diluted $ 8.50 $ 7.47 14 %
Non-GAAP net income(a) $ 1,182 $ 1,127 5 %
Non-GAAP net income per share – diluted(a) $ 10.24 $ 9.77 5 %

"I am pleased with the performance of our business in the second quarter of 2023, including incremental pipeline progress and exceptional commercial execution," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "We continue to prioritize internal investments while allocating additional capital to opportunistic share repurchases and potential business development."

Business Highlights

Key Pipeline Progress
Regeneron has approximately 35 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

Aflibercept 8 mg

In June 2023, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for the Biologics License Application (BLA) for aflibercept 8 mg for the treatment of patients with neovascular age-related macular degeneration (wet AMD), DME, and diabetic retinopathy (DR). The CRL was issued solely due to unresolved observations resulting from an FDA inspection at a third-party contract manufacturing organization, Catalent, that the Company engaged to complete vial-filling for aflibercept 8 mg. The CRL did not identify any issues with the aflibercept 8 mg clinical efficacy or safety profile, trial design, labeling, or drug substance manufacturing, and no additional clinical data or trials have been requested. The FDA has informed the Company and Catalent that certain manufacturing data and other information are required from Catalent to allow the FDA to approve aflibercept 8 mg; the Company expects that these data and information will be submitted to the FDA by mid-August 2023. The FDA has stated that it intends to prioritize the review of this submission, and therefore the Company anticipates the FDA will take action on the aflibercept 8 mg BLA during the third quarter of 2023.
In June 2023, the Company announced top-line, two-year (96 weeks) data for aflibercept 8 mg from the pivotal PHOTON trial in patients with DME. The longer-term data among aflibercept 8 mg patients who completed the trial demonstrated that the vast majority of patients were able to maintain or further extend the dosing intervals through two years. In addition, visual gains for aflibercept 8 mg remained consistent with those observed in the first year of the trial. In PHOTON, the safety of aflibercept 8 mg continued to be similar to EYLEA through two years and remained consistent with the known safety profile of EYLEA from previous clinical trials for DME. Results from the PHOTON study were presented at the American Society of Retina Specialists annual meeting in July 2023.
The two-year data from the pivotal PULSAR trial for aflibercept 8 mg in wet AMD continue to be expected in the third quarter of 2023.
In May 2023, Bayer announced that it initiated a Phase 3 study to evaluate the efficacy and safety of aflibercept 8 mg at extended dosing intervals compared to the standard of care, EYLEA, in macular edema following retinal vein occlusion (RVO).
Dupixent (dupilumab)

The FDA granted Breakthrough Therapy designation for uncontrolled COPD with an eosiniphilic phenotype based on the positive results of the Phase 3 BOREAS study. Based on ongoing discussions with the FDA, the Company expects that in addition to the BOREAS study results, data from the replicate Phase 3 NOTUS study will be needed to support an sBLA, and such data requirements remain under discussion with the FDA. The Company expects final results for the NOTUS study in mid-2024.
The Company and Sanofi presented positive Phase 3 results from the BOREAS trial in adults currently on maximal standard-of-care inhaled therapy (triple therapy) with uncontrolled COPD and evidence of type 2 inflammation at the 2023 American Thoracic Society International Conference. The results were also published in the New England Journal of Medicine.
In June 2023, the Ministry of Health, Labour and Welfare (MHLW) in Japan approved Dupixent for the treatment of adult patients with prurigo nodularis.
Oncology Programs

The Company announced promising data from three independent expansion cohorts of a Phase 1 trial for fianlimab, an antibody to LAG-3, in combination with Libtayo (cemiplimab) in adults with advanced melanoma, which were also presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. These results demonstrated that the combination led to clinically meaningful and durable results across multiple advanced melanoma patient populations. The safety profile of the combination was generally consistent with the safety profile of Libtayo monotherapy and other anti-PD-(L)1 agents, except for higher rates of adrenal insufficiency, which were successfully managed with steroid replacement.
The Company also presented updated positive data from two expansion dose cohorts from a pivotal trial for linvoseltamab, a bispecific antibody targeting BCMA and CD3, in patients with heavily pre-treated, relapsed/refractory multiple myeloma at the ASCO (Free ASCO Whitepaper) Annual Meeting. No new safety signals were identified.
The Company is investigating multiple CD28 costimulatory bispecific antibodies, including PSMAxCD28, EGFRxCD28, MUC16xCD28, and CD22xCD28, in ongoing Phase 1 trials in a variety of tumor settings in combination with Libtayo, or in combination with corresponding CD3 bispecifics. In the ongoing study of REGN5678, a costimulatory bispecific antibody targeting PSMA and CD28 in advanced prostate cancer, the Company has observed antitumor activity in combination with Libtayo as well as with REGN5678 monotherapy. In the Libtayo combination cohort, there have now been two immune-mediated Grade 5 adverse events (death), including one in July 2023. As a result, the Company has discontinued enrollment of patients receiving the combination of REGN5678 and full-dose Libtayo, and plans to explore REGN5678 combinations with lower doses of Libtayo. The Company also plans to enroll patients in a REGN5678 monotherapy cohort, as well as in combination with other immunotherapy modalities. Other costimulatory bispecific development programs continue their respective dose-escalation studies.
Itepekimab, an antibody to IL-33

The Phase 3 program investigating itepekimab in patients with COPD who are former smokers passed a recent interim futility analysis. The analysis was conducted by an Independent Data Monitoring Committee, and the Company and Sanofi remain blinded to the data. Results from the AERIFY-1 and AERIFY-2 studies are expected to be reported in 2025.

Corporate Update

The United States Supreme Court issued a unanimous opinion, ending a nearly decade-long patent dispute related to Praluent (alirocumab). The decision affirms the United States Court of Appeals for the Federal Circuit’s opinion, which held that Amgen’s asserted U.S. PCSK9 patent claims were invalid.
Second Quarter 2023 Financial Results

Revenues

($ in millions) Q2 2023 Q2 2022 % Change
Net product sales:
EYLEA – U.S. $ 1,500 $ 1,621 (7 %)
Libtayo – U.S. 130 91 43 %
Libtayo – ROW 80 — *
Praluent – U.S. 41 31 32 %
Evkeeza – U.S. 19 11 73 %
Inmazeb – U.S. 2 — *
Total net product sales 1,772 1,754 1 %

Collaboration revenue:
Sanofi 944 678 39 %
Bayer 377 358 5 %
Other (4 ) 8 *
Other revenue 69 59 17 %
Total revenues $ 3,158 $ 2,857 11 %

* Percentage not meaningful.
Net product sales of EYLEA in the U.S. decreased in the second quarter of 2023, compared to the second quarter of 2022, primarily due to a lower net selling price driven by changing market dynamics, including increased competition.

Sanofi collaboration revenue increased in the second quarter of 2023, compared to the second quarter of 2022, primarily due to the Company’s share of profits from commercialization of antibodies, which were $751 million in the second quarter of 2023, compared to $497 million in the second quarter of 2022. The change in the Company’s share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales.

Refer to Table 4 for a summary of collaboration revenue.

Operating Expenses

GAAP %
Change
Non-GAAP(a) %
Change
($ in millions) Q2 2023 Q2 2022 Q2 2023 Q2 2022
Research and development (R&D) $ 1,085 $ 794 37 % $ 974 $ 690 41 %
Acquired in-process research and development (IPR&D) $ — $ 197 (100 %) * * n/a
Selling, general, and administrative (SG&A) $ 652 $ 476 37 % $ 562 $ 418 34 %
Cost of goods sold (COGS) $ 192 $ 149 29 % $ 163 $ 137 19 %
Cost of collaboration and contract manufacturing (COCM) $ 213 $ 148 44 % * * n/a
Other operating (income) expense, net $ (1 ) $ (17 ) (94 %) * * n/a

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded.
GAAP and non-GAAP R&D expenses increased in the second quarter of 2023, compared to the second quarter of 2022, driven by additional costs incurred in connection with higher headcount and headcount-related costs, the advancement of the Company’s late-stage pipeline, the impact of the 2022 amendments to the Sanofi collaboration agreements, and increased manufacturing activity associated with the Company’s earlier-stage product candidates.
Acquired IPR&D in the second quarter of 2022 included a $195 million charge related to the Company’s acquisition of Checkmate Pharmaceuticals, Inc.
GAAP and non-GAAP SG&A expenses increased in the second quarter of 2023, compared to the second quarter of 2022, primarily due to an increase in commercialization-related expenses for Libtayo outside the U.S. (as effective July 1, 2022, the Company became solely responsible for the commercialization of Libtayo worldwide), higher headcount and headcount-related costs, and higher contributions to an independent not-for-profit patient assistance organization.
COCM expenses increased in the second quarter of 2023, compared to the second quarter of 2022, primarily due to the recognition of costs in connection with manufacturing commercial supplies of Dupixent.
Other Financial Information

GAAP other income (expense) included the recognition of net unrealized losses on equity securities of $31 million in the second quarter of 2023, compared to $164 million in the second quarter of 2022. GAAP and Non-GAAP other income (expense) also included interest income of $118 million in the second quarter of 2023, compared to $28 million in the second quarter of 2022.

In the second quarter of 2023, the Company’s GAAP effective tax rate (ETR) was 10.6%, compared to 11.5% in the second quarter of 2022. In the second quarter of 2023, the non-GAAP ETR was 12.2%, compared to 13.6% in the second quarter of 2022.

GAAP net income per diluted share was $8.50 in the second quarter of 2023, compared to $7.47 in the second quarter of 2022. Non-GAAP net income per diluted share was $10.24 in the second quarter of 2023, compared to $9.77 in the second quarter of 2022. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

During the second quarter of 2023, the Company repurchased shares of its common stock and recorded the cost of the shares, or $723 million, as Treasury Stock. As of June 30, 2023, an aggregate of $2.3 billion remained available for share repurchases under the Company’s share repurchase program.

On August 3, 2023 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported a corporate update and financial results for the second quarter ending June 30, 2023 (Press release, PTC Therapeutics, AUG 3, 2023, View Source [SID1234633771]).

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"I am extremely proud of the revenue growth in the first half of 2023 providing us confidence that we will meet our full-year total revenue guidance," said Matthew Klein, M.D., Chief Executive Officer, PTC Therapeutics, Inc. "In addition, the great results from the APHENITY and PIVOT-HD trials position us well for future growth."

Key Corporate Updates:

Second quarter 2023 revenue for the Duchenne muscular dystrophy (DMD) franchise was $162 million, representing 21% year-over-year growth.
Translarna (ataluren) quarterly net product revenue was $96 million, with growth coming from treatment of new patients and continued geographic expansion.
Emflaza (deflazacort) quarterly net product revenue was $66 million, driven by new patients, and high compliance.
Key Clinical and Regulatory Updates:

The primary endpoint of blood phenylalanine reduction in the APHENITY trial for sepiapterin in PKU was achieved, with highly statistically significant and clinically meaningful results.
PTC expects to file an NDA for sepiapterin in the fourth quarter of 2023, pending FDA feedback.
All key objectives were met in the 12-week interim data analysis of the PIVOT-HD trial of PTC518 in Huntington’s disease patients.
PTC expects to submit the BLA for Upstaza in the third quarter of 2023.
PTC expects a CHMP opinion on the Type II variation to support the conversion of the conditional marketing authorization for Translarna to a standard marketing authorization in the third quarter of 2023.
PTC expects additional regulatory meetings in the second half of 2023 including:
Type C meeting with the FDA for vatiquinone in FA
Type C meeting with the FDA for Translarna in DMD
Second Quarter 2023 Financial Highlights:

Total revenues were $213.8 million for the second quarter of 2023, compared to $165.5 million for the second quarter of 2022.
Total revenues include net product revenue across the commercial portfolio of $174.6 million for the second quarter of 2023, compared to $143.7 million for the second quarter of 2022. Total revenues also include royalty and manufacturing revenue of $39.2 million for the second quarter of 2023, compared to $21.8 million for the second quarter of 2022.
Translarna net product revenues were $96.5 million for the second quarter of 2023, compared to $77.0 million for the second quarter of 2022. These results were driven by treatment of new patients and continued geographic expansion.
Emflaza net product revenues were $65.7 million for the second quarter of 2023, compared to $56.8 million for the second quarter of 2022. These results reflect new patients and high compliance.
Roche reported Evrysdi 2023 year-to-date sales of approximately CHF 705 million, resulting in royalty revenue of $36.9 million to PTC for the second quarter of 2023, as compared to $21.8 million for the second quarter of 2022.
Based on U.S. GAAP (Generally Accepted Accounting Principles), GAAP R&D expenses were $185.9 million for the second quarter of 2023, compared to $157.3 million for the second quarter of 2022. The increase primarily reflects additional investment in advancement of the clinical pipeline.
Non-GAAP R&D expenses were $170.3 million for the second quarter of 2023, excluding $15.5 million in non-cash, stock-based compensation expense, compared to $143.5 million for the second quarter of 2022, excluding $13.8 million in non-cash, stock-based compensation expense.
GAAP SG&A expenses were $88.4 million for the second quarter of 2023, compared to $79.9 million for the second quarter of 2022. The increase reflects our continued investment to support commercial activities, including expanding our commercial portfolio.
Non-GAAP SG&A expenses were $74.6 million for the second quarter of 2023, excluding $13.8 million in non-cash, stock-based compensation expense, compared to $66.0 million for the second quarter of 2022, excluding $13.9 million in non-cash, stock-based compensation expense.
During the second quarter of 2023, PTC announced the discontinuation of preclinical and early research programs in gene therapy and a reduction in workforce as part of a strategic portfolio prioritization, which resulted in a one-time charge of approximately $8.0 million recorded to R&D and SG&A expense.
The change in the fair value of contingent consideration was a gain of $128.9 million for the second quarter of 2023, compared to a gain of $15.2 million for the second quarter of 2022. The change in fair value of contingent consideration is related to the fair valuation of potential future consideration to be paid to former equity holders of Agilis Biotherapeutics, Inc. (Agilis) in connection with PTC’s acquisition of Agilis, which closed in August 2018. As a result of the discontinuation of the Friedreich ataxia and Angelman syndrome gene therapy programs, PTC determined that the fair value for all of the contingent consideration payable related to Friedreich ataxia and Angelman syndrome was $0 and recorded a gain of $129.8 million, which is the primary driver of the overall gain during the quarter. An intangible asset impairment of $217.8 million was recorded in the second quarter of 2023 which also related to the discontinuation of Friedreich ataxia and Angelman syndrome gene therapy programs. The net impact of these gene therapy program discontinuations was non-cash expense of $88 million recorded within total operating expenses.
The net loss was $198.9 million for the second quarter of 2023, compared to a net loss of $152.1 million for the second quarter of 2022.
Cash, cash equivalents, and marketable securities was $337.9 million on June 30, 2023, compared to $410.7 million at December 31, 2022.
Shares issued and outstanding as of June 30, 2023, were 75,318,233.
PTC Updates Full Year 2023 Financial Guidance as Follows:

PTC anticipates total revenues for the full year 2023 to be between $940 million and $1.0 billion.
PTC anticipates net product revenues for the DMD franchise for the full year 2023 to be between $545 and $575 million.
PTC anticipates GAAP R&D and SG&A expense for the full year 2023 to be between $930 million and $980 million.
PTC anticipates Non-GAAP R&D and SG&A expense for the full year to be between $810 million and $860 million, excluding estimated non-cash stock-based compensation expense of $120 million.
PTC also anticipates up to $62 million of one-time expenses, paid in cash or equity ($37 million of which was incurred during the first half of 2023), upon achievement of potential clinical and regulatory success-based milestones from previous acquisitions and expenses associated with a rights exchange agreement.