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ENHERTU® ▼ (TRASTUZUMAB DERUXTECAN) AUTHORISED IN THE UK FOR THE TREATMENT OF HER2 POSITIVE METASTATIC BREAST CANCER

On February 16, 2021 Daiichi Sankyo UK, Limited (hereafter, Daiichi Sankyo) and AstraZeneca UK reported its Enhertu (trastuzumab deruxtecan) has been granted conditional authorisation in the UK as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens (Press release, Daiichi Sankyo, FEB 16, 2021, View Source [SID1234575132]).

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In the UK, almost 54,000 cases of breast cancer in women are diagnosed annually, with an estimated one in five cases being HER2 positive.1,2,3 The impact of the disease is significant, with breast cancer responsible for approximately 12,000 deaths per year.1 There are an estimated 35,000 people living with metastatic breast cancer in the UK, and in around 5% of women the breast cancer has already spread by the time it is diagnosed.4

"One in five women with breast cancer have HER2 positive disease. Though significant treatment advances have been made, there has been no clear standard of care for patients with metastatic HER2 positive disease following progression on first and second-line treatment and many patients do not have a durable response to other available later-line treatment options," said Dr Rebecca Roylance, Consultant Medical Oncologist, UCLH. "The authorisation of trastuzumab deruxtecan by the MHRA and EMA brings a new treatment option to patients and their doctors in the UK."

Authorisation is based on the results of the single arm, phase 2 DESTINY-Breast01 trial of trastuzumab deruxtecan (5.4 mg/kg) in 184 patients with HER2 positive metastatic breast cancer. Results from the data cut-off in June 2020 demonstrated a confirmed objective response rate of 61.4% (95% CI: 54.0-68.5), including a 6.5% complete response rate and a 54.9% partial response rate. After a median follow-up of 20.5 months, the median duration of response (DoR) was 20.8 months (95% CI: 15.0-NR).5 Trastuzumab deruxtecan showed a generally tolerable safety profile with 33 (17.9%) treatment discontinuations due to treatment-emergent adverse events.6

"Trastuzumab deruxtecan offers an important new option for patients with HER2 positive metastatic breast cancer in the UK who are in need of new treatment options after their cancer has progressed beyond both 1st and 2nd line therapy," said Haran Maheson, Commercial Director for Oncology, Daiichi Sankyo U.K. "This authorisation by the MHRA and EMA is the first for a medicine using our proprietary Dxd antibody drug conjugate technology and highlights the strength of the Daiichi Sankyo and AstraZeneca collaboration. We will now work closely in partnership with the MHRA to fulfil all regulatory requirements before stock can be available in the UK."

"The DESTINY-Breast01 trial showed a duration of response not previously seen in patients after progression on 1st and 2nd line treatment," said Arun Krishna, Head of Oncology, AstraZeneca U.K. "Trastuzumab deruxtecan is an important new treatment option for patients at this stage of care and will shift clinical discussions towards a focus on targeted treatment. This is the first new cancer medicine to be authorised by the MHRA in 2021 and our focus now is on securing access for NHS patients as quickly as possible."

The safety of trastuzumab deruxtecan has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2 positive breast cancer who received at least one dose of trastuzumab deruxtecan 5.4 mg/kg in clinical studies. The median duration of exposure to trastuzumab deruxtecan was 9.8 months (range: 0.7 to 37.1 months). The most common adverse reactions were nausea (79.9%), fatigue (60.3%), vomiting (48.7%), alopecia (46.2%), constipation (35.9%), decreased appetite (34.6%), anaemia (33.8%), neutropenia (32.5%), diarrhoea (30.8%), thrombocytopenia (23.1%), cough (21.4%), leukopenia (20.5%), and headache (20.1%).5

Cases of interstitial lung disease (ILD) or pneumonitis were reported in 15.0% (n=234) of patients. Fatal outcomes were observed in 3% of patients. Patients should be advised to immediately report cough, dyspnoea, fever, and/or any new or worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD or pneumonitis and those with suspected ILD or pneumonitis should be evaluated by radiographic imaging, preferably a computed tomography (CT) scan. Patients with a history of ILD or pneumonitis may be at increased risk.5

Appraisals of trastuzumab deruxtecan by the National Institute of Health and Care Excellence and the Scottish Medicines Consortium are currently underway and NHS access decisions are expected later in 2021.

About HER2 positive breast cancer
HER2 is an epidermal growth factor receptor expressed on the surface of many types of tumours including breast cancer. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and poor prognosis in breast cancer.7

There remain significant unmet clinical needs for patients with HER2 positive metastatic breast cancer, since the disease remains incurable with patients eventually progressing after currently available treatment options.8,9

About DESTINY-Breast01
DESTINY-Breast01 is a phase 2, single-arm, open-label, global, multicentre, two-part trial evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2 positive unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2-based regimens, including trastuzumab emtansine (100%), trastuzumab (100%), and pertuzumab (65.8%). The primary endpoint of the trial is confirmed objective response rate, as determined by independent central review. Key secondary objectives were the disease control rate, clinical-benefit rate, duration of response and progression-free survival and safety.

About trastuzumab deruxtecan
Trastuzumab deruxtecan is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy (‘payload’) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Trastuzumab deruxtecan is comprised of a humanised anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.

Trastuzumab deruxtecan (5.4 mg/kg) has also been granted conditional approval in the EU, under accelerated approval, as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens based on the DESTINY-Breast01 trial.

About the collaboration between Daiichi Sankyo and AstraZeneca
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise trastuzumab deruxtecan in March 2019, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan.

HOOKIPA Pharma to Participate in Upcoming SVB Leerink Global Healthcare Conference

On February 16, 2021 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that HOOKIPA’s management team will participate in the upcoming virtual SVB Leerink Global Healthcare Conference (Press release, Hookipa Pharma, FEB 16, 2021, View Source [SID1234575131]):

Fireside Discussion: Thursday, February 25, 2021 at 9:20 AM ET
The live audio webcast of the presentation will be available within the Investors & Media section of HOOKIPA’s website at View Source An archived replay will be accessible for 30 days following the event.

Cancer Genetics Announces Closing of $17.5 Million Common Stock Offering Priced At-the-Market under Nasdaq Rules

On February 16, 2021 Cancer Genetics, Inc. (the "Company") (Nasdaq: CGIX), a leader in drug discovery and preclinical oncology and immuno-oncology services, reported the closing of its previously announced registered direct offering with several healthcare-focused institutional investors of 2,777,778 shares of its common stock at a purchase price of $6.30 per share, priced at-the-market under Nasdaq rules (Press release, Cancer Genetics, FEB 16, 2021, View Source [SID1234575126]). The gross proceeds to the Company from the offering totaled approximately $17.5 million, before deducting placement agent fees and offering expenses.

H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

The Company currently intends to use the net proceeds from the offering for general corporate purposes, including working capital and capital expenditures. The net proceeds are also expected to be available to the combined company once the previously announced merger with StemoniX closes, which is subject to stockholder approval.

The shares described above were offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-239497) filed with the Securities and Exchange Commission (SEC) on June 26, 2020 and declared effective on July 21, 2020. The offering of the securities described herein was made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the securities being offered was filed with the SEC. Electronic copies of the final prospectus supplement and accompanying prospectus may be obtained on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (646) 975-6996, or email at [email protected].

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

Entry into a Material Definitive Agreement

On February 16, 2021, Kadmon Holdings, Inc. (the "Company") reported that entered into an indenture (the "Indenture"), dated as of February 16, 2021, between the Company and U.S. Bank National Association, as trustee (the "Trustee"), relating to the issuance of $240,000,000 principal amount of the Company’s 3.625% Convertible Senior Notes due 2027 (the "Notes") in an offering conducted in accordance with Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Filing, 8-K, Kadmon, FEB 16, 2021, View Source [SID1234575125]). The Company granted the initial purchasers 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 $40,000,000 principal amount of Notes. The initial purchasers have exercised this option in full. The net proceeds from the offering, after deducting the initial purchasers’ discounts, but before deducting estimated offering expenses (which include expenses related to the capped call transactions, as described below) were $232.8 million.

The Notes will bear interest at a rate of 3.625% per year. Interest will be payable semi-annually in arrears on February 15 and August 15 of each year, beginning on August 15, 2021. The Notes will mature on February 15, 2027, unless earlier repurchased, redeemed or converted. Before November 15, 2026, noteholders will have the right to convert their Notes only upon the occurrence of certain events. From and after November 15, 2026, noteholders may convert their Notes at any time at their election until the close of business on the second scheduled trading day immediately before the maturity date. The Company 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 the Company’s election. The initial conversion rate is 143.7815 shares of common stock per $1,000 principal amount of Notes, which represents an initial conversion price of approximately $6.96 per share of common stock. The conversion rate and conversion price will be subject to customary adjustments upon the occurrence of certain events. In addition, if certain corporate events that constitute a "Make-Whole Fundamental Change" (as defined in the Indenture) occur, then the conversion rate will, in certain circumstances, be increased for a specified period of time.

The Company may not redeem the Notes at its option at any time before February 20, 2024. The Notes will be redeemable, in whole or in part, at the Company’s option at any time, and from time to time, on or after February 20, 2024 and on or before the 40th 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 the Company’s common stock exceeds 130% of the conversion price on (i) each of at least 20 trading days, whether or not consecutive, during the 30 consecutive trading days ending on, and including, the trading day immediately before the date the Company sends the related redemption notice; and (ii) the trading day immediately before the date the Company sends such notice. In addition, calling any Note for redemption will constitute a Make-Whole Fundamental Change with respect to that Note, in which case the conversion rate applicable to the conversion of that Note will be increased in certain circumstances if it is converted after it is called for redemption.

If certain corporate events that constitute a "Fundamental Change" (as defined in the Indenture) occur, then, subject to a limited exception for certain cash mergers, noteholders may require the Company to repurchase their Notes at a cash repurchase price equal to the principal amount of the Notes to be repurchased, plus accrued and unpaid interest, if any, to, but excluding, the fundamental change repurchase date. The definition of Fundamental Change includes certain business combination transactions involving the Company and certain de-listing events with respect to the Company’s common stock.

The Notes have customary provisions relating to the occurrence of "Events of Default" (as defined in the Indenture), which include, but are not limited to, the following: (i) certain payment defaults on the Notes (which, in the case of a default in the payment of interest on the Notes, will be subject to a 30-day cure period); (ii) the Company’s failure to send certain notices under the Indenture within specified periods of time; (iii) the Company’s failure to comply with certain covenants in the Indenture relating to the Company’s ability to consolidate with or merge with or into, or sell, lease or otherwise transfer, in one transaction or a series of transactions, all or substantially all of the consolidated assets of the Company and its subsidiaries, taken as a whole, to another person; (iv) a default by the Company in its other obligations or agreements under the Indenture or the Notes if such default is not cured or waived within 60 days after notice is given in accordance with the Indenture; (v) certain defaults by the Company or any of its significant subsidiaries with respect to indebtedness for borrowed money of at least $20,000,000; (vi)

certain defaults by the Company or any of its significant subsidiaries with respect to one or more final judgments of at least $25,000,000; and (vii) certain events of bankruptcy, insolvency and reorganization involving the Company or any of the Company’s significant subsidiaries.

If an Event of Default involving bankruptcy, insolvency or reorganization events with respect to the Company (and not solely with respect to a significant subsidiary of the Company) occurs, then the principal amount of, and any accrued and unpaid interest on, all of the Notes then outstanding will immediately become due and payable without any further action or notice by any person. If any other Event of Default occurs and is continuing, then, the Trustee, by notice to the Company, or noteholders of at least 25% of the aggregate principal amount of Notes then outstanding, by notice to the Company and the Trustee, may declare the principal amount of, and any accrued and unpaid interest on, all of the Notes then outstanding to become due and payable immediately. However, notwithstanding the foregoing, the Company may elect, at its option, that the sole remedy for an Event of Default relating to certain failures by the Company to comply with certain reporting covenants in the Indenture consists exclusively of the right of the noteholders to receive special interest on the Notes for up to 360 days at a specified rate per annum equal to 0.25% of the principal amount of the Notes for the first 180 days and, thereafter, at a rate per annum equal to 0.50% on the principal amount of the Notes.

The above description of the Indenture and the Notes is a summary and is not complete. A copy of the Indenture and the form of the certificate representing the Notes are filed as exhibits 4.1 and 4.2, respectively, to this Current Report on Form 8-K, and the above summary is qualified by reference to the terms of the Indenture and the Notes set forth in such exhibits.

Onconova Therapeutics, Inc. Announces Closing of $28.75 Million Public Offering of
Common Stock Including Full Exercise of the Over-Allotment Option

On February 16, 2021 Onconova Therapeutics, Inc. (NASDAQ: ONTX) ("Onconova"), a biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the closing of its previously-announced underwritten public offering (Press release, Onconova, FEB 16, 2021, View Source [SID1234575124]). A total of 28,750,000 shares of its common stock were sold, including 3,750,000 shares of common stock following the exercise by the underwriters of their over-allotment option, at a public offering price of $1.00 per share. The gross proceeds of the offering to the Company are $28.75 million, before deducting the underwriting discounts and commissions and other estimated offering expenses.

Guggenheim Securities is acting as sole book-running manager. Maxim Group LLC and Noble Capital Markets, Inc. are acting as co-managers for the offering.

The securities described above were offered by Onconova pursuant to a shelf registration statement on Form S-3 (File No. 333-237844) which was initially filed by the Company with the Securities and Exchange Commission ("SEC") on April 24, 2020, amended on Form S-3/A that was filed with the SEC on May 15, 2020, and was declared effective by the SEC on May 18, 2020.

A preliminary prospectus supplement relating to the offering was filed with the SEC on February 10, 2021 and is available on the SEC’s website at View Source A final prospectus supplement relating to and describing the terms of the offering was filed with the SEC and is also available on the SEC’s website at View Source Copies of the final prospectus supplement and accompanying prospectus relating to the offering may be obtained from Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of 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 securities laws of any such state or jurisdiction.