On June 29, 2022 Celleron Therapeutics, the UK-based company developing innovative precision cancer medicines, reported a 3-year survival rate of 7.3% in late-stage micro-satellite stable colorectal cancer patients in their Phase II clinical trial, following treatment with zabadinostat (a potentially best-in-class HDAC inhibitor) and nivolumab (an immune checkpoint inhibitor commonly used to treat MSI CRC but has no activity in MSS CRC).

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The Phase II clinical trial (CAROSELL study) investigates the effect of zabadinostat (formerly CXD101) in combination with nivolumab in MSS colorectal cancer, which does not respond to immune checkpoint inhibitors (ICI) alone. The clinical strategy is well supported by scientific evidence showing how zabadinostat upregulates genes involved in antigen presentation and activity of natural killer cells, thus attracting cytotoxic T-cells to tumours and killing cells through the immune system; in essence, "turning cold tumours hot".

Following a dose confirmation safety run-in, which showed no treatment-induced toxicity, a Phase II recommended dose (P2RD) of zabadinostat and nivolumab was selected for further investigation. The patients in the study had advanced or metastatic disease, having relapsed after at least two previous lines of therapy.

Enrolment to the Phase II study was completed in May 2019, and all ongoing subjects have completed study treatment. Of 46 evaluable MSS CRC subjects, 22 (48%) exhibited durable disease control (stable disease plus partial response).

Post-treatment survival analysis is still ongoing, with surviving patients now under standard of care. The median Overall Survival (OS) was 7 months. Of all patients treated, 8/55 (14.5%) remained in survival 2 years from first dose. To date, 4/55 (7.3%) patients continue to survive past the three-year follow-up point.

Safety wise, the study combination was well tolerated. The most frequent observed Adverse Events were fatigue, nausea, and cytopenia. All AEs were manageable. There were no deaths or discontinuations from the study due to adverse drug reactions.

In consideration to the mechanism of action, clinical activity and safety, the results in this Phase II study suggest that zabadinostat plus nivolumab may be a superior treatment in advanced MSS CRC than marketed products, such as Lonsurf and Stivarga.

David Kerr, CMO of Celleron Therapeutics and Professor of Cancer Medicine at the University of Oxford, commented:

"We are pleased to continue seeing evidence that zabadinostat and nivolumab may prolong survival in very late-stage cancer patients, with some surviving past three years, the significance of which cannot be understated. This Phase II study not only strengthens the argument that zabadinostat is a clinically viable drug, but perhaps also the best-in-class treatment for cold tumours, such as MSS CRC which do not respond to treatment with immune checkpoint drugs. We remain dedicated to deploying zabadinostat as a precision medicine, maximising clinical benefit by using immune biomarkers to improve selection of patients – a key deliverable of our upcoming Phase III study".

NOTES:
About Colorectal Cancer

Colorectal cancer is the second most common tumour type in women, and the third most common in men, globally. The approximate 5-year survival rate for colorectal cancer patients in the United States is 10% for those with advanced metastatic disease (Stage IV).

Surgery is indicated for localised disease, whilst chemotherapy has been the standard management for patients with metastatic colorectal cancer. Two agents have been approved for third line management of advanced colorectal cancer, namely regorafenib and Trifluridine-tipiracil hydrochloride (Lonsurf).

A subset (5%) of colorectal cancers is characterized with deficient DNA mismatch repair (dMMR or microsatellite instability, MSI). These tumours tend to have a high expression of checkpoint proteins (PD-1 and PD-L1), which interfere with the body’s normal anti-tumour T-cell response. By disabling these proteins, immune checkpoint inhibitors (ICI) such as nivolumab allow the immune system to function properly, and T-cells to kill tumour cells.

However, for the greater majority of patients with a normal Mismatch Repair proficient expression, the microsatellite phenotype is stable (MSS), antigen presentation is believed to be much decreased, and the tumour is thus resistant to checkpoint inhibition. Most MSS patients will ultimately relapse or become resistant to chemotherapy. Thus, there remains a very significant unmet clinical need to find novel agents, singly and/or in combination, for the treatment of these late-stage patients.

On June 29, 2022 Cytokinetics, Incorporated ("Cytokinetics") (Nasdaq: CYTK) reported its intention to offer, subject to market and other conditions, $450.0 million aggregate principal amount of convertible senior notes due 2027 (the "notes") in a private offering to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Cytokinetics, JUN 29, 2022, View Source [SID1234616412]). Cytokinetics also expects to grant the initial purchasers of the notes an option to purchase, for settlement within a period of 13 days from, and including, the date the notes are first issued, up to an additional $90.0 million aggregate principal amount of notes.

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The notes will be senior, unsecured obligations of Cytokinetics and will accrue interest payable semi-annually in arrears. The notes will mature on July 1, 2027, unless earlier converted, redeemed or repurchased by Cytokinetics. Noteholders will have the right to convert their notes in certain circumstances and during specified periods. Cytokinetics will settle conversions by paying or delivering, as applicable, cash, shares of its common stock or a combination of cash and shares of its common stock, at Cytokinetics’ election. The notes will be redeemable, in whole or in part (subject to certain limitations), at Cytokinetics’ option at any time, and from time to time, on or after July 6, 2025 and, in the case of any partial redemption, on or before the 60th scheduled trading day immediately before the maturity date, at a cash redemption price equal to the principal amount of the notes to be redeemed, plus accrued and unpaid interest, if any, to, but excluding, the redemption date, but only if the last reported sale price per share of Cytokinetics’ common stock exceeds 130% of the conversion price for a specified period of time. The interest rate, initial conversion rate and other terms of the notes will be determined at the pricing of the offering.

Cytokinetics intends to use a portion of the net proceeds from the offering and to issue shares of its common stock to repurchase a portion of its outstanding 4.00% convertible senior notes due 2026 (the "2026 notes") through privately negotiated transactions entered into concurrently with the pricing of the offering. The terms of any repurchases of the 2026 notes will depend on factors, including the market price of Cytokinetics’ common stock and the trading price of the 2026 notes at the time of such repurchases.

Cytokinetics intends to use the remainder of the net proceeds of this offering to (a) expand and support its clinical development program for aficamten in patients with hypertrophic cardiomyopathy ("HCM"), including the spending associated with the potential conduct of a second Phase 3 clinical trial in patients with obstructive HCM and a first Phase 3 clinical trial in patients with non-obstructive HCM; (b) expand commercial capabilities and conduct readiness activities in the United States, Canada and Europe to support the potential launch of omecamtiv mecarbil and aficamten in those geographies; (c) advance its early stage clinical development pipeline, including the progression of CK-136 to proof of concept studies and the potential development of additional cardiac myosin inhibitors for the potential treatment of heart failure with preserved ejection fraction ("HFpEF"); (d) expand its muscle biology focused research activities to energetics, growth and metabolism of muscle, and (e) for general corporate purposes, including working capital.

In connection with any repurchase of the 2026 notes, Cytokinetics expects that holders of the outstanding 2026 notes that have hedged their equity price risk with respect to the 2026 notes (the "hedged holders") will, concurrently with the pricing of the notes, unwind their hedge positions by buying Cytokinetics’ common stock and/or entering into or unwinding various derivative transactions with respect to its common stock. The amount of common stock to be purchased by the hedged holders may be substantial in relation to the historic average daily trading volume of Cytokinetics’ common stock. This activity by the hedged holders may increase the effective conversion price of the notes.

The offer and sale of the notes and any shares of common stock issuable upon conversion of the notes have not been, and will not be, registered under the Securities Act or any other securities laws, and the notes and any such shares may not be offered or sold except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and any other applicable securities laws.

This press release does not constitute an offer to sell, or the solicitation of an offer to buy, the notes or any shares of common stock issuable upon conversion of the notes, nor will there be any sale of the notes or any such shares, in any state or other jurisdiction in which such offer, sale or solicitation would be unlawful.

On June 29, 2022, Exact Sciences Corporation (the "Company"), reported that through a wholly-owned special purpose entity, Exact Receivables LLC ("Exact Receivables"), entered into an accounts receivable securitization program (the "Securitization Facility") with PNC Bank, National Association ("PNC"), as administrative agent, with a scheduled maturity date of June 29, 2024 (Filing, 8-K, Exact Sciences, JUN 29, 2022, View Source [SID1234616407]). The Securitization Facility provides Exact Receivables with up to $150.0 million of borrowing capacity, subject to maintaining certain borrowing base requirements, by collateralizing the customer accounts receivable of Exact Sciences Laboratories, LLC and Genomic Health, Inc.

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PNC serves as the lender pursuant to a Loan Agreement with the Company dated November 5, 2021, under which a revolving line of credit of up to $150.0 million is available to the Company, until a scheduled termination date of November 5, 2023.

On June 29, 2022, Exact Receivables borrowed $50.0 million under the Securitization Facility.

Outstanding loans under the Securitization Facility accrue interest at a rate equal to a daily SOFR rate, a term SOFR rate or a base rate, in any case, plus an applicable margin. Additionally, Exact Receivables will pay certain fees to the agents and the lenders under the Securitization Facility.

The Securitization Facility contains certain customary representations, warranties, affirmative covenants and negative covenants, subject to certain cure periods in some cases, including the eligibility of the receivables, as well as customary reserve requirements, events of default, termination events, and servicer defaults. The Securitization Facility termination events permit the lenders to terminate the Receivables Financing Agreement upon the occurrence of certain specified events, including, among others, failure by Exact Receivables to pay amounts when due, certain defaults on other material indebtedness, certain judgments, a change of control, certain events negatively affecting the overall credit quality of transferred receivables and bankruptcy and insolvency events.

The Securitization Facility consists of, among other agreements, (i) a Receivables Financing Agreement (the "Receivables Financing Agreement") among Exact Receivables, PNC, as administrative agent, and the lenders and other parties party thereto, (ii) a Receivables Purchase Agreement (the "Company Purchase Agreement") among the Company and certain subsidiaries of the Company and (iii) a Receivables Purchase Agreement (the "Borrower Purchase Agreement") among Exact Receivables and the Company. The foregoing descriptions of the Receivables Financing Agreement, the Company Purchase Agreement and the Borrower Purchase Agreement do not purport to be complete and are qualified in their entirety by reference to the full text of such agreements, copies of which are filed herewith as Exhibit 10.1, Exhibit 10.2, and Exhibit 10.3, respectively, and the terms of which are incorporated herein by reference.

On June 29, 2022, Seres Therapeutics, Inc. (the "Company") reported that entered into a Securities Purchase Agreement with certain institutional accredited investors (the "IAIs") named therein (the "Non-Affiliate Purchase Agreement") and a Securities Purchase Agreement with certain directors and officers of the Company (the "Affiliates", and collectively with the IAIs, the "Purchasers") named therein (the "Affiliate Purchase Agreement" and, together with the Non-Affiliate Purchase Agreement, the "Purchase Agreements") (Filing, 8-K, Seres Therapeutics, JUN 29, 2022, View Source [SID1234616399]). Pursuant to the Purchase Agreements, the Company agreed to issue and sell in a registered direct offering (the "Offering") (i) an aggregate of 31,238,094 shares of the Company’s common stock, par value $0.001 per share (the "Common Stock"), at a purchase price of $3.15 per share (the "Purchase Price") to the IAIs, for aggregate gross proceeds to the Company of $98.4 million, and (ii) an aggregate of 507,936 shares of Common Stock at the Purchase Price to the Affiliates, for aggregate gross proceeds to the Company of $1.6 million, in each case pursuant to an effective shelf registration statement on Form S-3, as amended (File No. 333-244401) and a related prospectus supplement filed with the Securities and Exchange Commission. The closing of the Offering is expected to occur on or about July 5, 2022, subject to the satisfaction of customary closing conditions.

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The Company expects to receive net proceeds from the Offering of approximately $96.8 million, after deducting the placement agent’s fees and estimated offering expenses payable by the Company. The Company intends to use the net proceeds from the Offering for commercial readiness and manufacture of SER-109 for the U.S. market, including expanding longer-term commercial manufacturing capacity, advancing the clinical development of SER-109 for the EU market, and other general corporate and working capital purposes. The Company believes that its existing cash, cash equivalents and investments, together with the net proceeds from the Offering, will fund its operations for at least 12 months from the date of the prospectus related to the Offering filed with the Securities and Exchange Commission (the "SEC") on June 30, 2022. This evaluation does not take into consideration contingent payments associated with SER-109 FDA approval, which the Company anticipates in the first half of 2023, as these are uncertain and there is no assurance the Company will receive them. These contingent payments include the potential to receive a $125 million milestone payment pursuant to the Company’s collaboration and license agreement with NHSc Pharma Partners upon SER-109 FDA approval and a $25 million tranche under its existing term loan with Hercules Capital, Inc., which becomes available upon the satisfaction of certain conditions, including FDA approval of SER-109.

The Purchase Agreements contain customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Purchasers, including for liabilities under the Securities Act of 1933, as amended (the "Securities Act"), other obligations of the parties and termination provisions.

The foregoing description of the Purchase Agreements is not complete and is qualified in its entirety by reference to the full text of the Non-Affiliate Purchase Agreement and Affiliate Purchase Agreement, forms of which are filed as Exhibits 10.1 and 10.2, respectively, to this Current Report on Form 8-K and are incorporated by reference herein.

On June 29, 2022 Exicure, Inc. (NASDAQ: XCUR), an early-stage biotechnology company focused on the development of next generation nucleic acid therapies targeting RNA to address both genetic and non-genetic neurological disorders and hair loss disorders, reported that, following the implementation of a one-for-thirty reverse stock split at 5:00 p.m. EDT today, the Company’s common stock will begin trading on a split-adjusted basis on Nasdaq effective with the open of business tomorrow, Thursday, June 30, 2022 (Press release, Exicure, JUN 29, 2022, View Source [SID1234616394]). The Company’s common stock will continue to trade under the ticker symbol "XCUR". The new CUSIP number for the post-reverse split common shares is 30205M 200. The Company is implementing the reverse stock split in an effort to regain compliance with Nasdaq’s minimum bid price requirement of $1.00 per share.

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As a result of the reverse stock split, every thirty pre-split shares of common stock outstanding will be automatically combined and converted into one issued and outstanding share of common stock, without any change in the par value per share. No fractional shares of the Company’s common stock will be issued to any stockholders in connection with the reverse stock split. Holders of record will receive a cash payment in lieu of fractional shares.

Stockholders of record will receive information regarding their share ownership from the Company’s transfer agent, American Stock Transfer & Trust Company, LLC. AST can be reached at (877) 248-6417 or (718) 921-8337.

As previously disclosed, on December 30, 2021, Nasdaq notified the Company that it no longer satisfied the minimum bid price requirement set forth in Nasdaq Listing Rule 5550(a)(2), as the bid price for the Company’s common stock had closed below $1.00 per share for the previous thirty consecutive business days (the "Bid Price Requirement"). In accordance with Nasdaq Listing Rule 5810(c)(3)(A), the Company was granted a 180-calendar day compliance period, through June 28, 2022, to regain compliance with the Bid Price Requirement. The Company did not do so within the time provided and, on June 29, 2022, was notified that the Company’s securities were subject to delisting unless the Company timely requested a hearing before the Nasdaq Hearings Panel (the "Panel"). The Company plans to timely request a hearing before the Panel, which will stay any further action by Nasdaq at least until the conclusion of the hearing process.

In any event, should the Company evidence compliance with the Bid Price Requirement for the requisite minimum ten-consecutive business day period prior to or following the hearing, the Company will request that Nasdaq issue a compliance determination, in which case the listing matter will be closed.