Sarepta Therapeutics Prices $1.0 Billion of Convertible Senior Notes Due 2027

On September 14, 2022 Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, reported the pricing of $980.0 million aggregate principal amount of convertible senior unsecured notes that will mature on September 15, 2027, unless earlier redeemed, repurchased or converted (Press release, Sarepta Therapeutics, SEP 14, 2022, View Source [SID1234619559]). The notes are being offered and sold only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Act") (the "Rule 144A offering"). Sarepta has also granted the initial purchasers of the notes an option to purchase up to an additional $150 million aggregate principal amount of notes. The sale of the notes to the initial purchasers is expected to settle on September 16, 2022, subject to customary closing conditions.

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An entity affiliated with a member of Sarepta’s Board of Directors has agreed to purchase $20 million aggregate principal amount of the notes in a separate concurrent private placement under Section 4(a)(2) of the Act (the "concurrent private placement" and together with the Rule 144A offering, the "offerings"). The offering of the notes in the Rule 144A offering is not conditioned upon the closing of the concurrent private placement, but the concurrent private placement is conditioned upon the closing of the Rule 144A offering.

Sarepta estimates that the net proceeds of the offerings will be approximately $979.4 million (or approximately $1.1 billion if the initial purchasers’ option to purchase additional shares is exercised in full), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses payable by Sarepta. Sarepta intends to use $110.7 million of the net proceeds from the offerings to pay the cost of the capped call transactions described below, and approximately $248.3 million to repurchase approximately $150.6 million in aggregate principal amount of its 1.50% Convertible Senior Notes due 2024 (the "2024 Notes"), inclusive of any applicable premium and accrued interest (described below). In addition, Sarepta intends to use approximately $585.5 million of the net proceeds from the offerings to repay borrowings under, to pay accrued and unpaid interest and prepayment fees under, and terminate its credit agreement and the remaining net proceeds to fund general corporate purposes. Sarepta anticipates that, along with current cash and projected revenue, this offering is sufficient to fund operations to profitability.

The notes will be senior, unsecured obligations of Sarepta and bear cash interest at a rate of 1.25%, payable on March 15 and September 15 of each year, beginning on March 15, 2023. The notes will be convertible, only during certain periods and subject to certain circumstances, into cash, shares of Sarepta’s common stock, or a combination of cash and shares of Sarepta’s common stock, at Sarepta’s election. The initial conversion rate for the notes is 7.0439 shares of Sarepta’s common stock per $1,000 principal amount of notes, which is equivalent to an initial conversion price of approximately $141.97 per share of Sarepta’s common stock, representing an approximately 35.0% conversion premium based on the last reported sale price of Sarepta’s common stock on September 13, 2022. Prior to September 20, 2025, the notes will not be redeemable. On or after September 20, 2025 and on or before the 41st scheduled trading day immediately preceding the maturity date, Sarepta may redeem for cash all or part of the notes (subject to certain conditions), at its option, if the last reported sale price of Sarepta’s common stock has been at least 130% of the conversion price then in effect for at least 20 trading days (whether or not consecutive), including the trading day immediately preceding the date on which Sarepta provides notice of redemption, during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which Sarepta provides notice of redemption.

In connection with the pricing of the notes and the concurrent private placement, Sarepta entered into privately negotiated capped call transactions with certain of the initial purchasers or their respective affiliates and certain other financial institutions (the "option counterparties"). The capped call transactions are expected generally to reduce the potential dilution to Sarepta’s common stock upon conversion of any notes and/or offset any potential cash payments Sarepta is required to make in excess of the principal amount of converted notes, as the case may be, subject to a cap. The cap price of the capped call transactions will initially be $210.32 per share, which represents a premium of 100.0% over the last reported sale price of Sarepta’s common stock of $105.16 per share on September 13, 2022, and is subject to certain adjustments under the terms of the capped call transactions. If the initial purchasers of the notes exercise their option to purchase additional notes, Sarepta expects to enter into additional capped call transactions with the option counterparties.

Sarepta has been advised that, in connection with establishing their initial hedges of the capped call transactions, the option counterparties or their respective affiliates expect to purchase shares of Sarepta’s common stock and/or enter into various derivative transactions with respect to Sarepta’s common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Sarepta’s common stock or the notes at that time. In addition, the option counterparties or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Sarepta’s common stock and/or by purchasing or selling Sarepta’s common stock or other securities of Sarepta’s in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so during any observation period related to a conversion of notes). This activity could also cause or avoid an increase or a decrease in the market price of Sarepta’s common stock or the notes, which could affect the ability of holders to convert the notes and, to the extent the activity occurs following conversion or during any observation period related to a conversion of the notes, it could affect the number of shares of Sarepta’s common stock and value of the consideration that holders will receive upon conversion of the notes.

Contemporaneously with the pricing of the notes in this offering, Sarepta entered into separate, privately negotiated transactions with certain holders of its 2024 Notes to repurchase approximately $150.6 million in aggregate principal amount of the 2024 Notes for approximately $248.3 million in cash, inclusive of any applicable premium and interest (the "concurrent note repurchases"). The terms of the concurrent note repurchases were individually negotiated with certain holders of the 2024 Notes.

Sarepta expects that holders of any 2024 Notes that Sarepta has agreed to repurchase that have hedged their equity price risk with respect to such notes (the "hedged holders") will, concurrently with or shortly after the pricing of the notes, unwind their hedge positions by buying Sarepta’s common stock and/or entering into or unwinding various derivative transactions with respect to Sarepta’s common stock.

In connection with the issuance of the 2024 Notes, Sarepta entered into capped call transactions (the "existing capped call transactions") with certain financial institutions (the "existing option counterparties"). Sarepta intends to enter into agreements with the existing option counterparties concurrently with or shortly after the closing of this offering to terminate a portion of the existing capped call transactions in a notional amount corresponding to the principal amount of the 2024 Notes repurchased in the concurrent note repurchases. In connection with any such termination of a corresponding portion of the existing capped call transactions, Sarepta expects that such existing option counterparties and/or their respective affiliates will sell shares of Sarepta’s common stock in secondary market transactions, and/or unwind various derivative transactions with respect to Sarepta’s common stock. In connection with such terminations, Sarepta anticipates that it will receive proceeds from the existing counterparties, which it intends to use for general corporate purposes.

Any repurchase of the 2024 Notes and the termination of a corresponding portion of the existing capped call transactions described above, and the potential related market activities by holders of the 2024 Notes participating in the concurrent note repurchases and the existing counterparties, as applicable, could increase (or reduce the size of any decrease in) or decrease (or reduce the size of any increase in) the market price of Sarepta’s common stock, which may affect the trading price of the notes at that time. Sarepta cannot predict the magnitude of such market activity or the overall effect it will have on the price of the notes or Sarepta’s common stock.

The offer and sale of the notes are not being registered under the Securities Act, or any state securities laws. The notes may not be offered or sold in the United States except pursuant to an exemption from the registration requirements of the Securities Act and any applicable state securities laws.

This news release does not constitute an offer to sell or a solicitation of an offer to buy the securities described herein, nor shall there be any sale of these securities, in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the laws of such jurisdiction.

TRACON Pharmaceuticals Announces Fast Track Designation by the FDA for Envafolimab for the Treatment of the Soft Tissue Sarcoma Subtypes of UPS and MFS

On September 14, 2022 TRACON Pharmaceuticals, Inc. (Nasdaq: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported that the U.S. Food and Drug Administration (FDA) has granted fast track designation for the development of envafolimab (KN035) for patients with locally advanced, unresectable or metastatic undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) who have progressed on one or two prior lines of chemotherapy (Press release, Tracon Pharmaceuticals, SEP 14, 2022, View Source [SID1234619557]).

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"We applied for fast track designation based on activity observed in the ENVASARC Phase 2 pivotal trial and are pleased to receive this notification from the FDA," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Soft tissue sarcoma is a disease in need of new treatments and we expect to provide data through the ENVASARC pivotal trial showing superior efficacy and safety of envafolimab compared to currently approved therapy for refractory soft tissue sarcoma. Accrual in the pivotal ENVASARC trial remains robust and we expect to report an independent data monitoring committee interim safety review [and interim efficacy review in the fourth quarter."

The FDA designed the fast track process to facilitate the development and expedite the review of drugs to treat serious or life-threatening diseases or conditions and fill unmet medical needs. Fast track designation can confer important benefits, including the potential eligibility for priority review of a Biologics License Application, if relevant criteria are met, as discussed in our Annual Report on Form 10-K for the year ended December 31, 2021.

About Envafolimab

Envafolimab (KN035), a single-domain antibody against PD-L1 invented by Alphamab Oncology and licensed by TRACON, is the first approved subcutaneously injected PD-(L)1 inhibitor. Envafolimab was approved by the Chinese NMPA in November 2021 in adult patients with MSI-H/dMMR advanced solid tumors who failed systemic treatment and have no satisfactory alternative treatment options. In December 2019, Alphamab Oncology, 3D Medicines and TRACON entered into a collaboration whereby TRACON has the right to develop and commercialize envafolimab in soft tissue sarcoma in North America. Envafolimab is currently being studied in the pivotal ENVASARC Phase 2 trial in the United States sponsored by TRACON and a Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China sponsored by TRACON’s corporate partners, Alphamab Oncology and 3D Medicines.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at 30 top cancer centers in the United States and the United Kingdom that began dosing in December 2020. TRACON expects the trial to enroll more than 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into a cohort of treatment with single agent envafolimab at 600 mg every three weeks and 80 patients enrolled into a cohort of treatment with envafolimab at 600 mg every three weeks with Yervoy. The primary endpoint is objective response rate by central review with duration of response a key secondary endpoint.

Surface Oncology to Present Preclinical Data Highlighting the IL-27 Gene Expression Signature in Treatment-Resistant Cancers at the 10th Annual International Cytokine and Interferon Society Meeting

On September 14, 2022 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that the company will present new preclinical data on the role of IL-27 in therapy resistance at the 10th Annual Cytokines Meeting of the International Cytokine and Interferon Society (ICIS) being held September 20 – 23 at Big Island, Hawaii (Press release, Surface Oncology, SEP 14, 2022, View Source [SID1234619556]). The poster, entitled IL-27 Inhibits Immune Cell Reinvigoration Mediated by PD-(L)1 Blockade and Induces a Type 1 Interferon Gene Expression Signature Associated with Resistance to Therapy in Cancer Patients (#297), will first be presented in a virtual preview session today at 2:00 – 3:30 pm HST/8:00 – 9:30 pm EDT.

"IL-27 is a key regulator in the immunosuppressive environment of a variety of tumors, and it can counteract T cell reinvigoration seen after PD-(L)1 pathway inhibition, thus preventing T cells from attacking the cancer cells," said Vito Palombella, chief scientific officer, Surface Oncology. "We have identified an IL-27 gene signature that is enriched in several tumor types from The Cancer Genome Atlas (TCGA). Interestingly, this IL-27 signature includes many interferon (IFN) stimulated genes that have been associated with resistance to therapy across different cancers. These findings further bolster our belief that SRF388, a first-in-class anti-IL-27 monoclonal antibody, holds important potential in the treatment of certain cancers."

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Summary of key data:

IL-27 induces the expression of several immunoregulatory receptors (e.g., PD-L1, TIM-3, LAG-3, and TIGIT) and reduces inflammatory cytokine production
An IFN-stimulated gene signature is expressed in a variety of human tumors and associated with resistance to cancer therapies including chemotherapy, radiotherapy, and immune checkpoint inhibition. These IFN-stimulated genes are also upregulated by IL-27.
IL-27 and Type 1 interferons (IFNα2, IFNβ1) counteract the immune cell reinvigoration seen after PD-(L)1 pathway blockade in human PBMCs, while IFNγ does not.
Loss of IL-27 function, through either genetic deficiency or pharmacologic inhibition by SRF388, a first-in-class anti-IL-27 monoclonal antibody, leads to tumor growth inhibition in mouse models and early clinical data have shown monotherapy activity of SRF388 in patients with cancer (NCT04374877).
Poster presentation details:

Title: IL-27 Inhibits Immune Cell Reinvigoration Mediated by PD-(L)1 Blockade and Induces a Type 1 Interferon Gene Expression Signature Associated with Resistance to Therapy in Cancer Patients
Poster number: 297
Virtual presentations: Wednesday, September 14, 2:00 – 3:30 pm HST/8:00 – 9:30 pm EDT and Thursday, September 15, 8:00 – 9:30 am HST/2:00 – 3:30 pm EDT
In-person session: Thursday, September 22, 4:00 – 5:30 pm HST
The poster can also be found on Surface Oncology’s website.

About SRF388
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver, kidney and lung cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA.

SELLAS Life Sciences to Participate in the Cantor Oncology, Hematology & HemeOnc Conference on September 28th

On September 14, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that Angelos Stergiou, MD, ScD. h.c, President and Chief Executive Officer of SELLAS, will participate in the Cantor Oncology, Hematology, HemeOnc Conference to be held at the Lotte New York Palace in New York City on Wednesday, September 28, 2022 (Press release, Sellas Life Sciences, SEP 14, 2022, View Source;HemeOnc-Conference-on-September-28th/default.aspx [SID1234619553]).

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Dr. Stergiou will participate in the ‘Leukemia and MDS’ panel at 3:25 p.m. Eastern Time.

For more information about the conference, or to schedule a one-on-one meeting with SELLAS management, please contact your Cantor representative directly, or send an email to KCSA Strategic Communications at [email protected].

QIAGEN and Neuron23 Partner to Develop Next-Generation Sequencing Companion Diagnostic for Novel Parkinson’s Disease Drug

On September 14, 2022 QIAGEN (NYSE:QGEN; Frankfurt Prime Standard: QIA) and Neuron23 Inc., an early stage biotechnology company focused on developing precision medicines for genetically defined neurological and immunological diseases, reported the signing of an agreement to develop a companion diagnostic for Neuron23’s brain penetrant leucine-rich repeat kinase (LRRK2) inhibitor for Parkinson’s disease (Press release, Qiagen, SEP 14, 2022, View Source [SID1234619552]).

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Under the new Master Collaboration Agreement, QIAGEN will develop and validate a clinical trial assay that will detect a combination of biomarkers discovered by Neuron23 that together predict the responsiveness of Parkinson’s disease to a LRRK2 inhibitor. The partnership will support the clinical development of Neuron23’s drug candidate that is currently in the late stages of preclinical development. Subject to further clinical development, the agreement also covers options for the future development of additional companion diagnostics.

Neuron23 joins a group of more than 25 leading pharmaceutical and biotechnology companies who have reached master collaboration agreements with QIAGEN to develop and commercialize companion diagnostic tests for their drug candidates – a deep pipeline of potential future products to advance precision medicine for the benefit of patients around the world.

The assay for this collaboration will be integrated into a next-generation sequencing (NGS) workflow that leverages QIAGEN’s Sample to Insight capabilities, including instrumentation, IVD sample preparation, library preparation and bioinformatics. The workflow is planned to be developed using the NextSeqTM 500 System as part of the NGS strategic collaboration between QIAGEN and Illumina. Based on Neuron23’s artificial intelligence (AI)-enabled drug discovery and biomarker platform, it will target a complex signature of 50 single nucleic polymorphisms (SNPs) for U.S. and European populations and eventually additional SNPs that are prevalent in Asian populations.

"The collaboration with Neuron23 shows the rapid momentum precision medicine is gaining in disease areas outside oncology," said Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics, at QIAGEN. "Our expertise in blood- and NGS-based molecular testing from Sample to Insight will enable Neuron23 to run a clinical trial for a drug candidate that may have the potential to modify the course of an inexorable neurodegenerative disease in a genetically defined population."

"This collaboration combines the leading expertise of Neuron23 in drug discovery, data science, and machine learning with QIAGEN’s long-standing experience and global leadership in companion diagnostic development. QIAGEN’s blood-based test will help to identify patients with Parkinson’s disease who are likely to respond to Neuron23’s LRRK2 inhibitor. The development of a companion diagnostic identifying this sub-population of Parkinson’s disease patients will de-risk the clinical development of Neuron23’s LRRK2 inhibitor and help identify individuals who may benefit from this disease-modifying therapy. We are excited to be working with an industry leader on the first companion diagnostic developed for Parkinson’s disease," said Nancy Stagliano, Ph.D., CEO of Neuron23.

No laboratory tests are currently available for the diagnosis of non-genetic cases for Parkinson’s disease. Usually, the disease is diagnosed based on medical history and neurological examination. Although no cure currently exists for Parkinson’s disease, therapies are used to alleviate some symptoms.

LRRK2 is a complex, multidomain protein found in neurons and many tissues and cell types throughout the body. Mutations in the LRRK2 gene are one of the most common causes of familial Parkinson’s disease and individuals who inherit gain of function mutations in LRRK2 are clearly at higher risk to develop the disease in later life. Additionally, there is emerging evidence that LRRK2 may play a role in a subset of the larger population of patients with non-familial Parkinson’s disease. Recent investigations have shown that small-molecule LRRK2 inhibitors can be neuroprotective, suggesting that therapies targeting LRRK2 could be beneficial in a larger population of patients.

QIAGEN is a pioneer in precision medicine and the global leader in collaborations with pharmaceutical and biotechnology companies to co-develop companion diagnostics, which detect clinically relevant genetic abnormalities to provide insights that guide clinical decision-making in diseases such as cancer. QIAGEN has an unmatched depth and breadth of technologies from NGS to polymerase chain reaction (PCR) and digital PCR (dPCR) for companion diagnostic development. QIAGEN has ten PCR based companion diagnostic indications that are FDA approved, including therascreen EGFR for non-small cell lung cancer (NSCLC), therascreen KRAS for colorectal cancer and NSCLC, therascreen FGFR for urothelial cancer, therascreen PIK3CA for breast cancer based on tissue or plasma samples and the therascreen BRAF kit for colorectal cancer.