Capstan Therapeutics Launches with $165 Million to Deliver on the Clinical Promise of Precise In Vivo Cell Engineering

On September 14, 2022 Capstan Therapeutics, Inc., a biotechnology company dedicated to developing and delivering precise in vivo cell engineering to patients, reported that launched with $165 million in financing to build on the foundational insights of world-renowned leaders in mRNA and cell therapy, combining the power of cell therapy with the precision of genetic medicines to help bring safer, first-in-class medicines to more patients in multiple indications (Press release, Capstan Therapeutics, SEP 14, 2022, View Source [SID1234619529]).

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Capstan’s foundational precision in vivo engineering technology builds on research conducted in the laboratories of world-renowned mRNA and cell therapy scientists at the University of Pennsylvania.

Capstan’s funding includes a recently closed $102 million Series A financing led by Pfizer Ventures and joined by Leaps by Bayer, Eli Lilly and Company, Bristol Myers Squibb, Polaris Partners, Alexandria Venture Investments, and all existing investors, which follows a $63 million seed financing led by Novartis Venture Fund and OrbiMed and joined by RA Capital, and Vida Ventures in November 2021.

Advancing Breakthrough Therapies through Precision in vivo Engineering

The company plans to use the funds to further its mission of advancing the clinical promise of cell-based therapies by enabling precise in vivo engineering of cells with payloads necessary to benefit patients across multiple disease categories. Capstan’s modular platform leverages the biological and technological expertise of its founding scientists and includes proprietary targeted lipid nanoparticles (tLNP) technology, a suite of targeting moieties to mediate cell type-specific uptake, and disease-specific mRNA payloads aimed at directly engineering, or ablating pathogenic cells through in vivo generated CAR T cells.

Capstan is prioritizing programs based on the potential to transform clinical standards of care. The company’s initial efforts will focus on developing first-in-class in vivo CAR therapies, with the goal to deliver treatments in an outpatient setting, for patients who have diseases for which there are no effective treatments. Capstan also plans to leverage its precision delivery and engineering technology to advance new therapies for certain monogenic blood disorders.

Visionary Team of Accomplished Executives Poised to Deliver a Transformational Approach

Capstan is also pleased to announce that Laura Shawver, Ph.D., has joined the company as President and Chief Executive Officer. Dr. Shawver brings more than 20 years of experience in executive leadership positions in oncology and other serious diseases to this role, most recently serving as CEO of Silverback Therapeutics and President and CEO of Synthorx.

"Our ambition at Capstan is to invent new clinical paradigms through targeted in vivo reprogramming of cells," said Dr. Shawver. "Our founding scientific and operational team is purpose-built to advance programs to the clinic that unite decades of combined experience in groundbreaking CAR therapies with the latest advances in mRNA delivery technology. We are also fortunate to have a distinguished investor syndicate that understands the cell therapy landscape and recognizes the potential of this innovative approach. I am thrilled to lead this team as we work toward making this vision a reality for patients."

"Laura is an exceptional leader with a well-established track record in drug development and passion for addressing unmet needs in oncology and other serious diseases," said Michael Baran, Ph.D., Partner, Pfizer Ventures. "We are delighted to have someone of Laura’s caliber captain this exciting next chapter for Capstan to help unlock the potential of this transformative approach for patients."

Dr. Shawver joins an accomplished leadership team of industry veterans who have been at the forefront of cell and gene therapy, including Adrian Bot, M.D., Ph.D., Chief Scientific Officer, formerly Global Head and Vice President of Translational Medicine at Kite, a Gilead Company and previously Chief Scientific Officer at Kite Pharma; and Priya Karmali, Ph.D., Chief Technology Officer, who has over two decades of experience in the field of lipid nanoparticle mediated nucleic acid delivery technologies.

Building on Pioneering Work of World-Renowned Scientific Founders

"Capstan builds on a deep history of collaborative research in mRNA-enabled and CAR-based medicines by our incredible group of scientific founders," said Christian Homsy, M.D., MBA, Capstan’s founding CEO. "The company was established to deliver on the promise of cell-based medicines, and with Laura at the helm, is well-positioned to make rapid progress towards clinical evaluation."

The company’s scientific founders include several of the experts from the University of Pennsylvania who authored two landmark studies establishing preclinical proof-of-concept for non-viral, in vivo CAR-T therapy that Capstan plans to develop and advance toward the clinic. A 2019 Nature publication demonstrated the preclinical use of ex vivo CAR-T cell therapy against FAP, a fibrosis-related target. A follow-on study published in Science earlier this year built on these earlier results and demonstrated the production of functional CAR-T cells in vivo in a mouse model following a single IV administration of an mRNA encoding an anti-FAP CAR packaged in CD5-targeted-LNPs. The scientific founders span diverse areas of research expertise:

Preclinical translation – Jonathan Epstein, M.D. and Haig Aghajanian, Ph.D. (Dr. Aghajanian is now a Capstan employee.)
Cell engineering – Carl June, M.D. and Bruce Levine, Ph.D.
mRNA and targeted LNP technologies – Drew Weissman, M.D., Ph.D. and Hamideh Parhiz, Pharm.D., Ph.D.
Immunology and Fibrosis – Ellen Puré, Ph.D. and Steven Albelda, M.D.
"Capstan is uniting several recent life science technological advances in a manner that can hopefully unlock the potential of these technologies to develop new medicines for patients across a wider range of diseases," said Drew Weissman, M.D., Ph.D., Co-Founder of Capstan, who serves as the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovation in the Perelman School of Medicine at the University of Pennsylvania, and co-recipient of the 2021 Lasker-DeBakey Clinical Medical Research Award.

"Research conducted at Penn demonstrates the tremendous promise of harnessing mRNA and targeted LNP delivery to train a patient’s body to make CAR-T cells in vivo, potentially creating new treatment options," said Jonathan Epstein, M.D., Chief Scientific Officer at Penn’s Perelman School of Medicine. "We believe this approach has the potential to make an important impact not only in oncology, but also in fibrosis and many other diseases. My fellow scientific co-founders and I all look forward to actively partnering with Capstan in our collaborative effort to develop medicines that may benefit patients around the world."

First participants imaged in SAR-Bombesin prostate cancer trial in Australia

On September 14, 2022 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that it has successfully imaged its first participants in the diagnostic 64Cu SAR-Bombesin trial (BOP) for patients with PSMA-negative prostate cancer in Australia (Press release, Clarity Pharmaceuticals, SEP 14, 2022, View Source [SID1234619524]).

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BOP (Copper-64 SAR Bombesin in Prostate Specific Membrane Antigen (PSMA) negative Prostate Cancer) is a Phase II investigator-initiated trial (IIT) in up to 30 patients led by Prof Louise Emmett at St Vincent’s Hospital, Sydney. The BOP trial is assessing the safety of 64Cu-SAR-Bombesin as well as looking at the diagnostic potential across two different groups of men:

Participants with suspected biochemical recurrence (BCR) of their prostate cancer who have negative PSMA positron emission tomography (PET) imaging scans or low PSMA expression disease.
Participants with metastatic castrate resistant prostate cancer (mCRPC) who are not eligible for PSMA therapy.
The trial is imaging with 64Cu SAR-Bombesin on the day of administration as well as at later timepoints.

Prof Louise Emmett (St Vincent’s Hospital Sydney), Principal Investigator in the BOP trial, commented, "We are very pleased to have recruited and imaged the first participants in this study. The SAR-Bombesin product is a promising target for a large patient population with a high unmet need and few treatments available to them. We are excited to now make the product available to a larger pool of patients under clinical trial conditions".

"SAR-Bombesin has already shown very promising data to date through a SAS case study1, demonstrating diagnostic imaging potential in PSMA-negative prostate cancer and highlighting potential utility of the product as a theranostic agent. We are now looking forward to further investigating the role of SAR-Bombesin in the better management of patients," said Prof Emmett.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "The commencement of this trial is yet another step forward in our collaboration with Prof Emmett and St Vincent Hospital Sydney as the BOP IIT is now our third clinical trial conducted in partnership. We are pleased that this collaboration has already resulted in changes in the management of the disease for patients in our own city of Sydney, as we head towards our ultimate goal of improving treatment outcomes for children and adults with cancer around the world."

"We believe that SAR-Bombesin has potential to provide large patient populations with accurate and precise detection and treatment of cancers that express the target and deliver clinical, environmental and logistical benefits enabled by the copper isotope pairing," said Dr Taylor.

Clarity’s Prostate Cancer clinical trial program overview

About SAR-Bombesin
SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the gastrin-releasing peptide receptor (GRPr) present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPr is found in approximately 75-100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)2-6. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide7. The National Cancer Institute estimates in 2022 there will be 268,490 new cases of prostate cancer in the US and around 34,500 deaths from the disease8.

Approximately 20% of prostate cancers with BCR are PSMA-PET negative9-12. These patients are therefore unlikely to respond to therapeutic PSMA-targeted products and currently have few treatment options available to them. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment. The SAR-Bombesin product could offer valuable imaging and therapeutic options for not only PSMA negative patients, but also the large number of patients that have the target receptor on their cancers.

METiS Announces Pan-RAF Inhibitor License Agreement with Voronoi

On September 13, 2022 METiS Therapeutics, a Boston-area company integrating drug discovery and delivery with AI and machine learning, reported they have entered a license agreement with Voronoi, Inc., a Korean company focused on precision medicine (Press release, METiS Therapeutics, SEP 13, 2022, View Source [SID1234648430]). Under the terms of this license agreement, METiS will receive exclusive license to develop and commercialize Voronoi’s pan-RAF inhibitor program worldwide. In exchange, Voronoi will receive up to $1.7 million in upfront cash and success-based near-term discovery milestones. Voronoi will also be eligible for success-based payment up to $480.5 million in development, regulatory and sales milestones and tiered royalties based on annual net sales.

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"We view this program as a potential best-in-class asset addressing high unmet clinical needs for Class II and Class III BRAF mutant cancer patients, particularly those with CNS metastasis," said Chris Lai, CoFounder and CEO of METiS Therapeutics. "We see it as a compelling proof-of-concept opportunity for our AiTEM platform to improve compound pharmacokinetics and deliver a differentiated profile, including CNS penetration. In addition, we view this as a foundational asset for our oncology portfolio."

BRAF is a protein kinase involved in cancer cell growth and BRAF mutations are the most common mutation found in tumor cells[1]. While several BRAF v600E inhibitors have been approved, this mutation only represents about 45% of total BRAF mutations, compared to Class II and III mutations which represent 55 percent of total BRAF mutations. This underscores the need for new therapeutic options in this space.

"We developed our structurally distinguished type II pan-RAF inhibitor to address unmet medical needs, and this partnership brings us closer to our goal of delivering this candidate to patients," says Daekwon Kim, CEO of Voronoi. "We are excited to partner with METiS’ seasoned team to continue on development of our pan-RAF inhibitor." added Daekwon."We developed our structurally distinguished type II pan-RAF inhibitor to address unmet medical needs, and this partnership brings us closer to our goal of delivering this candidate to patients," says Daekwon Kim, CEO of Voronoi. "We are excited to partner with METiS’ seasoned team to continue on development of our pan-RAF inhibitor." added Daekwon.

This news follows METiS’ announcement that the company had joined the Roche Accelerator earlier this year. In December, METiS closed an $86 million Series A financing round. The company recently leased 14,000 square feet of mixed office and laboratory space at 101 Cambridgepark Drive in Cambridge, MA.14,

Entry into a Material Definitive Agreement

On September 13, 2022, Sarepta Therapeutics, Inc. (the "Company") reported that entered into a Purchase Agreement (the "Purchase Agreement") with the several initial purchasers named in Schedule 1 thereto (the "Initial Purchasers"), for whom Goldman Sachs & Co. LLC and J.P. Morgan Securities LLC acted as representatives (the "Representatives") relating to the sale of $980.0 million aggregate principal amount of 1.250% Convertible Senior Notes due 2027 (the "Offered Notes") to the Initial Purchasers (Filing, 8-K, Sarepta Therapeutics, SEP 13, 2022, View Source [SID1234619660]). The Company also granted the Initial Purchasers an option to purchase up to an additional $150.0 million aggregate principal amount of the Offered Notes, which option was exercised in full on September 14, 2022. The Purchase Agreement includes customary representations, warranties and covenants. Under the terms of the Purchase Agreement, the Company has agreed to indemnify the Initial Purchasers against certain liabilities.

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The foregoing description of the Purchase Agreement does not purport to be complete and is qualified in its entirety by reference to the Purchase Agreement, which is filed as Exhibit 10.1 to this Current Report on Form 8-K and is incorporated herein by reference.

Affiliated Investor Purchase Agreement

On September 13, 2022, the Company entered into a purchase agreement (the "Affiliated Investor Purchase Agreement") with Michael A. Chambers Living Trust (the "Affiliated Investor"), an entity affiliated with Michael Chambers, a member of the Company’s board of directors, to issue and sell $20.0 million in aggregate principal amount of 1.250% Convertible Senior Notes due 2027 (the "Affiliated Investor Notes" and together with the Offered Notes, the "Notes") in a private placement pursuant to an exemption from the registration requirements of the Securities Act of 1933, amended (the "Securities Act") afforded by Section 4(a)(2) of the Securities Act. The Affiliated Investor Purchase Agreement includes customary representations, warranties and covenants by the Company and customary closing conditions.

The foregoing description of the Affiliated Investor Purchase Agreement does not purport to be complete and is qualified in its entirety by reference to the Affiliated Investor Purchase Agreement, which is filed as Exhibit 10.2 to this Current Report on Form 8-K and is incorporated herein by reference.

Indenture and the Notes

The Notes were issued by the Company on September 16, 2022 pursuant to an Indenture, dated as of such date (the "Indenture"), between the Company and U.S. Bank Trust Company, National Association, as trustee (the "Trustee"). The Notes bear cash interest at the annual rate of 1.250%, payable on March 15 and September 15 of each year, beginning on March 15, 2023, and will mature on September 15, 2027 unless earlier redeemed, converted or repurchased. The Company will settle conversions of the Notes through payment or delivery, as the case may be, of cash, shares of common stock of the Company or a combination of cash and shares of common stock, at the Company’s option (subject to, and in accordance with, the settlement provisions of the Indenture). The initial conversion rate for the Notes is 7.0439 shares of common stock (subject to adjustment as provided for in the Indenture) per $1,000 principal amount of Notes, which is equivalent to an initial conversion price of approximately $141.97 per share of the Company’s common stock, representing an approximately 35.0% conversion premium on the closing price of the Company’s common stock of $105.16 per share 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, the Company may redeem for cash all or part of the Notes (subject to certain conditions), at its option, if the last reported sale price of the Company’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 the Company provides notice of redemption, during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which the Company provides notice of redemption. If the Company elects to redeem fewer than all of the outstanding Notes, at least $150.0 million aggregate principal amount of Notes must be outstanding and not subject to redemption as of, and after giving effect to, delivery of the relevant notice of redemption.

Holders of the Notes may convert their Notes at their option at any time prior to the close of business on the business day immediately preceding March 15, 2027 in multiples of $1,000 principal amount, only under the following circumstances:


during any calendar quarter commencing after the calendar quarter ending on December 31, 2022 (and only during such calendar quarter), if the last reported sale price of the Company’s common stock for at least 20 trading days (whether or not consecutive) during a period of 30 consecutive trading days ending on, and including, the last trading day of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price for the Notes on each applicable trading day;


during the five business day period after any five consecutive trading day period (the "measurement period") in which the "trading price" (as defined in the Indenture) per $1,000 principal amount of Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale price of the Company’s common stock and the conversion rate for the Notes on each such trading day;


if we call any or all of the notes for redemption, at any time prior to the close of business on the scheduled trading day immediately prior to the redemption date, but only with respect to the notes called (or deemed called) for redemption; or


upon the occurrence of specified corporate events described in the Indenture.

On or after March 15, 2027, until the close of business on the second scheduled trading day immediately preceding September 15, 2027, holders may convert their Notes, in multiples of $1,000 principal amount, at the option of the holder regardless of the foregoing circumstances.

If the Company experiences a fundamental change or gives a notice of redemption with respect to any or all of the Notes, as described in the Indenture, prior to the maturity date of the Notes, holders of the Notes will, subject to specified conditions, have the right, at their option, to require the Company to repurchase for cash all or a portion of their Notes at a repurchase price equal to 100% of the principal amount of the Notes to be repurchased, plus accrued and unpaid interest, if any, to, but not including, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date of the Notes, the Company will increase the conversion rate for a holder who elects to convert its Notes in connection with such corporate event.

The Indenture provides for customary events of default. In the case of an event of default with respect to the Notes arising from specified events of bankruptcy or insolvency, all outstanding Notes will become due and payable immediately without further action or notice. If any other event of default with respect to the Notes under the Indenture occurs or is continuing, the Trustee or holders of at least 25% in aggregate principal amount of the then outstanding Notes may declare the principal amount of the Notes to be immediately due and payable.

In certain circumstances if, at any time during the six-month period beginning on, and including, the date that is six months after the last date of original issuance of the Offered Notes, the Company fails to timely file certain documents or reports required under the Securities Exchange Act of 1934, as amended, or the Offered Notes are not otherwise freely tradable by holders of the Offered Notes other than the Company’s affiliates, additional interest will accrue on the Offered Notes during the period in which its failure to file has occurred and is continuing or such Offered Notes are not otherwise freely tradable by holders other than the Company’s affiliates.

In addition, if, and for so long as, the restrictive legend on the Offered Notes has not been removed, the Offered Notes are assigned a restricted CUSIP number or the Offered Notes are not otherwise freely tradable by holders other than the Company’s affiliates (without restrictions pursuant to U.S. securities laws or the terms of the Indenture or the Notes) as of the 380th day after the last date of original issuance of the Notes, the Company will pay additional interest on the Offered Notes during the period in which the Offered Notes remain so restricted.

The foregoing description of the Indenture and the Notes does not purport to be complete and is qualified in its entirety by reference to each of the Indenture and form of Note, which are filed as Exhibits 4.1 and 4.2 to this Current Report on Form 8-K and are incorporated herein by reference.

Capped Call Transactions

In connection with the issuance of the Notes, on September 13, 2022, the Company entered into privately negotiated capped call transactions with Barclays Bank PLC, Goldman Sachs & Co. LLC, Mizuho Markets Americas LLC, Morgan Stanley & Co. LLC, and RBC Capital Markets, LLC (each, a "Counterparty," and together the "Counterparties," and such transactions, the "Base Capped Call Transactions"). In connection with the Initial Purchasers’ exercise in full of their option to purchase additional Notes, on September 14, 2022, the Company entered into additional capped call transactions with the Counterparties (together with the Base Capped Call Transactions, the "Capped Call Transactions").

The Capped Call Transactions have an initial strike price of approximately $141.97 per share, which corresponds to the initial conversion price of the Notes and is subject to anti-dilution adjustments generally similar to those applicable to the Notes, and have a cap price of approximately $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. The Capped Call Transactions cover, subject to anti-dilution adjustments, 8,100,485 shares of the Company’s common stock, which is the same number of shares of the Company’s common stock initially underlying the Notes.

The Capped Call Transactions are expected generally to reduce the potential dilution to the Company’s common stock upon conversion of the Notes in the event that the market price per share of the Company’s common stock, as measured under the terms of the Capped Call Transactions, is greater than the strike price of the Capped Call Transactions as adjusted pursuant to the anti-dilution adjustments. If, however, the market price per share of the Company’s common stock, as measured under the terms of the Capped Call Transactions, exceeds the cap price of the Capped Call Transactions, there would nevertheless be dilution upon conversion of the Notes to the extent that such market price exceeds the cap price of the Capped Call Transactions.

The Company has been advised that, in connection with establishing their initial hedges of the Capped Call Transactions, the Counterparties or their respective affiliates may purchase shares of the Company’s common stock and/or entered into various derivative transactions with respect to the Company’s common stock, in each case, concurrently with, or shortly after, the pricing of the Notes. This activity may impact the market price of the Company’s common stock or the Notes.

In addition, the Company has been advised that the Counterparties or their respective affiliates may modify their hedge positions by entering into or unwinding various derivative transactions with respect to the Company’s common stock and/or by purchasing or selling the Company’s common stock or other securities of the Company 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 the Notes). This activity could also cause or avoid an increase or a decrease in the market price of the Company’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 the Company’s common stock and value of the consideration that holders will receive upon conversion of the Notes.

The Company intends to exercise options it holds under the Capped Call Transactions whenever Notes are converted on or after March 15, 2027, and expects that upon any conversions of Notes prior to March 15, 2027, or any repurchase of Notes by the Company, a corresponding portion of the Capped Call Transactions will be terminated. Upon such termination, the Company expects to receive from the Counterparties shares of its common stock, cash, or a combination thereof, in each case, with an aggregate market value equal to the then current value of the Capped Call Transactions or portion thereof, as the case may be, being early terminated, subject to the terms of the Capped Call Transactions. As a result, the Company may not receive the full expected benefit of the Capped Call Transactions. The Company has been advised that the Counterparties or their respective affiliates, in order to unwind their hedge positions with respect to those exercised or terminated options, are likely to buy or sell shares of the Company’s common stock or other securities or instruments of the Company, including the Notes, in secondary market transactions or unwind various derivative transactions with respect to such common stock. These unwind activities could have the effect of increasing or decreasing the trading price of the Company’s common stock and the Notes and could have the effect of increasing or decreasing the value of the consideration that holders of the Notes will receive upon conversion of the Notes.

The Capped Call Transactions are separate transactions entered into by and between the Company and the Counterparties and are not part of the terms of the Notes. Holders of the Notes will not have any rights with respect to the Capped Call Transactions.

The description of the Capped Call Transactions in this report is a summary and is qualified in its entirety by the terms of each of the confirmations for the Capped Call Transactions filed as Exhibits 10.3, 10.4, 10.5, 10.6, 10.7, 10.8, 10.9, 10.10, 10.11 and 10.12 to this Current Report on Form 8-K, which are incorporated herein by reference.

POINT Biopharma Prices Public Offering of Common Stock

On September 13, 2022 POINT Biopharma Global Inc. (NASDAQ: PNT) (the "Company" or "POINT"), a company accelerating the discovery, development and global access to life-changing radiopharmaceuticals, reported the pricing of its public offering of 13,900,000 shares of Common Stock at a public offering price of $9.00 per share (Press release, Point Biopharma, SEP 13, 2022, View Source [SID1234619558]). The gross proceeds to the Company from the offering, before deducting underwriting discounts and commissions and other estimated offering expenses, are expected to be approximately $125 million. In addition, the Company has granted the underwriters a 30-day option to purchase up to an additional 2,085,000 shares of its Common Stock. All of the shares to be sold in the offering are to be sold by POINT. The offering is expected to close on or about September 16, 2022, subject to customary closing conditions.

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Piper Sandler and Guggenheim Securities, LLC are acting as joint book-running managers for the offering. Oppenheimer & Co. is acting as lead manager for the offering.

POINT intends to use the net proceeds from the proposed offering, together with its existing cash, cash equivalents and investments, to fund clinical and preclinical research and development programs, pre-commercialization activities, and for working capital and other general corporate purposes.

The securities are being offered by POINT pursuant to a registration statement on Form S-3 previously filed and declared effective by the Securities and Exchange Commission ("SEC"). A preliminary prospectus supplement and accompanying prospectus relating to the proposed offering has been filed with the SEC and is available for free on the SEC’s website at View Source Copies of the preliminary prospectus supplement and the accompanying prospectus relating to these securities may also be obtained for free from:

Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924 or by email at [email protected].

Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544 or by email at [email protected].

Oppenheimer & Co., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, NY 10004, or by telephone at (212) 667-8055, or by email at [email protected].

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