On March 31, 2022 The Company reported that entered into an At Market Issuance Sales Agreement (the "Agreement") with Ladenburg Thalmann & Co. Inc. ("Ladenburg"). Under the Agreement, the Company may offer and sell its common stock, par value $0.001 per share, from time to time having an aggregate offering price of up to $25,000,000 (the "Shares") during the term of the Agreement through Ladenburg (Filing, 8-K, Tocagen, MAR 31, 2022, View Source [SID1234611354]). The Company has filed a prospectus supplement relating to the offer and sale of the Shares pursuant to the Agreement covering sales of up to $7,000,000 of Shares. The Shares will be issued pursuant to the Company’s previously filed and effective Registration Statement on Form S-3 (File No. 333-256611), which was initially filed with the Securities and Exchange Commission on May 28, 2021, and declared effective on June 7, 2021. The Company intends to use the net proceeds from the offering, if any, for general corporate purposes, including funding existing and potential new clinical programs.

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The Company is not obligated to sell any Shares pursuant to the Agreement. Subject to the terms and conditions of the Agreement, Ladenburg will use commercially reasonable efforts, consistent with its normal trading and sales practices and applicable state and federal law, rules and regulations and the rules of The Nasdaq Capital Market ("Nasdaq"), to sell Shares from time to time based upon the Company’s instructions, including any price, time or size limits or other customary parameters or conditions the Company may impose.

Under the Agreement, Ladenburg may sell Shares by any method permitted by law deemed to be an "at the market offering" as defined in Rule 415 of the Securities Act of 1933, as amended, and the rules and regulations thereunder, including, without limitation, sales made directly on or through Nasdaq, on or through any other existing trading market for the Shares or to or through a market maker. If expressly authorized by the Company, Ladenburg may also sell Shares in negotiated transactions.

The Agreement will terminate upon the earlier of (i) the issuance and sale of all of the Shares through Ladenburg on the terms and subject to the conditions set forth in the Agreement or (ii) termination of the Agreement as otherwise permitted thereby. The Agreement may be terminated at any time by either party.

The Company has agreed to pay Ladenburg a commission equal to 3.0% of the gross proceeds from the sales of Shares pursuant to the Agreement and has agreed to provide Ladenburg with customary indemnification and contribution rights.

The foregoing summary of the Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed as Exhibit 10.1 hereto and incorporated herein by reference. The Agreement contains representations and warranties that the parties made to, and solely for the benefit of, the other in the context of all of the terms and conditions of the Agreement and in the context of the specific relationship between the parties. The provisions of the Agreement, including the representations and warranties contained therein, are not for the benefit of any party other than the parties to the Agreement and are not intended as a document for investors and the public to obtain factual information about the Company’s current state of affairs. Rather, investors and the public should look to other disclosures contained in the Company’s filings with the SEC.

The opinion of the Company’s counsel regarding the validity of the Shares that may be issued pursuant to the Agreement is filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy Shares, nor shall there be any sale of the Shares 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.

On March 31, 2022, United Therapeutics Corporation (the "Company") reported that entered into a Credit Agreement (the "Credit Agreement") with certain of its subsidiaries party thereto, as guarantors (the "Guarantors"), the lenders referred to therein, and Wells Fargo Bank, National Association ("Wells Fargo"), as administrative agent and as a swingline lender (Filing, 8-K, United Therapeutics, MAR 31, 2022, View Source [SID1234611348]). The Credit Agreement provides for (i) an unsecured, revolving credit facility of up to $1.2 billion; and (ii) a second unsecured, revolving credit facility of up to $800 million (which facilities may, subject to obtaining commitments from existing or new lenders for such increase and subject to other condition, be increased by up to $500 million in the aggregate). The facilities mature five years after the closing date of the Credit Agreement, subject to an ability of the lenders thereunder, or certain of the lenders thereunder, to elect to extend the maturity date of their commitments by one year following a request for such extension by the Company in accordance with the terms of the Credit Agreement, up to a maximum of two such extensions.

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As of March 31, 2022, Lung Biotechnology PBC is the only subsidiary of the Company required to be a Guarantor and guarantee the Company’s obligations under the Credit Agreement. From time to time, one or more additional subsidiaries of the Company may be required to guarantee the Company’s obligations under the Credit Agreement.

At the Company’s option, the loan will bear interest at either an adjusted Term SOFR rate or a fluctuating base rate, in each case, plus an applicable margin that is determined on a quarterly basis based on the Company’s consolidated total leverage ratio (as calculated in accordance with the Credit Agreement).

The proceeds of borrowings under the Credit Agreement are available to refinance certain existing indebtedness of the Company and its subsidiaries and/or for working capital and other general corporate purposes. Upon closing of the Credit Agreement on March 31, 2022, the Company borrowed $800.0 million under the Credit Agreement, and used the funds to repay outstanding indebtedness under the 2018 Credit Agreement discussed under Item 1.02 below.

The Credit Agreement also contains customary affirmative and negative covenants that, among other things, limit the ability of the Company and its subsidiaries to: (a) incur indebtedness; (b) grant liens; (c) enter into a merger, consolidation, or amalgamation; (d) liquidate, wind up, or dissolve; or (e) sell all or substantially all of the property, business, or assets of the Company and its subsidiaries taken as a whole. In addition, as of the last day of each fiscal quarter, the Company must not permit (i) a consolidated ratio of total indebtedness to EBITDA to be greater than 3.00 to 1.00 (which ratio may, upon consummation of certain qualifying acquisitions, be increased to 3.50 to 1.00 for four fiscal quarters following such acquisition); and (ii) its consolidated interest coverage ratio to be less than 3.00 to 1.00, in each case calculated in accordance with the Credit Agreement.

The Credit Agreement contains customary events of default, including a change of control. Upon the occurrence and continuation of an event of default, all amounts due under the Credit Agreement and the other loan documents become (in the case of a bankruptcy event), or may become (in the case of all other events of default and at the option of the lenders), immediately due and payable.

On March 31, 2022 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to defeating cancer using RNA therapeutics, reported financial results for 2021 and recent business progress (Press release, TransCode Therapeutics, MAR 31, 2022, View Source [SID1234611344]).

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"2021 was a foundational year for TransCode, highlighted by our successful IPO on Nasdaq in July," said Michael Dudley, co-founder, president and CEO of TransCode. "With resources from the IPO, as well an important Small Business Innovation Research (SBIR) grant, we drove significant progress across the organization, including key additions to our team that bring valuable expertise, and continued advancement of our lead candidate and our preclinical development programs. We are now building on this foundation as we move toward clinical development which we expect will demonstrate the power and versatility of our TTX platform in solving the challenges of RNA delivery in oncology."

TransCode Therapeutics co-founder and Chief Technology Officer, Dr. Zdravka Medarova, added, "We are on track to submit an exploratory Investigational New Drug Application (eIND) this year to test our lead therapeutic candidate, TTX-MC138, in a Phase 0 study in metastatic solid tumors. We believe this study has the potential to establish proof-of-mechanism for our platform, upon which we hope to build a broad and diverse pipeline of therapeutics and diagnostics with the potential to reach previously undruggable genetic targets."

Key 2021 Highlights

·Completed an over-subscribed initial public offering on Nasdaq in July, raising gross proceeds of $28.8 million; the Company’s outstanding convertible promissory notes were converted into common stock upon completion of the IPO.

·Expanded the leadership team with the appointment of TransCode’s scientific co-founder, Zdravka Medarova, Ph.D., as Chief Technology Officer effective October 1. Dr. Medarova is a leader in the field of non-coding RNA delivery to cancer and has authored multiple high-impact publications on the topic of RNA delivery, nanotechnology, and the biology of cancer metastasis. Leadership team further strengthened in 2021 with additional key appointments, including:

Susan Duggan as VP of Clinical Operations, Dustan Bonnin as VP of Corporate Strategy and Subrata Ghosh, Ph.D, as Principal Scientist; and
Dejan Juric, M.D., appointed to the Scientific Advisory Board. Dr. Juric, a renowned expert in personalized cancer medicine and a breast cancer specialist, serves as director of the Henri and Belinda Termeer Center for Targeted Therapies and Investigational Cancer Therapeutics Program at Massachusetts General Hospital.

·Awarded a Fast-Track Small Business Innovation Research (SBIR) grant from National Institutes of Health (NIH), totaling $2.3 million. The award is a fast track award based on milestones achievement, to support the clinical evaluation of TTX-MC138, including translational experiments to identify and optimize a method for measuring miR-10b expression in breast cancer clinical samples, as well as IND-enabling activities and measurement of delivery of TTX-MC138.

Expected Upcoming Milestones

TransCode’s goals to continue to advance its portfolio include:

·TTX-MC138

Submission to FDA of an eIND application for First-in-Human (FIH) clinical trial.
Initiation of a FIH Phase 0 clinical study evaluating delivery of TTX-MC138 to metastatic lesions in 10 Stage IV patients with solid tumors
Concurrent completion of IND-enabling studies to support filing of an IND application for a Phase I clinical trial of TTX-MC138.

·Publication of preclinical results supporting the lead therapeutic candidate TTX-MC138 in pancreatic cancer and glioblastoma multiforme.

·Continuation of preclinical studies for therapeutic candidates TTX-RIGA, TTX-siPDL1, and TTX-siLin28b.

2021 Financial Highlights (in millions)

•Cash: $ 20.8
•R&D Expenses: $ 2.8
•G&A Expenses: $ 3.4
•Operating Loss: $ 6.8

Financial Guidance

TransCode expects that its cash of $20.8 million as of December 31, 2021, together with additional funding expected from an April 2021 SBIR award, are sufficient to fund planned operations into the first quarter 2023 but not for a full 12 months from the date of our financial statements.

Conference Call

The Company will host an investor conference call at 4:30 p.m. ET on April 7, 2022. A question-and-answer session will follow management’s presentation.

If you are unable to participate during the live call, the call will be recorded and later made available on the Company’s website.

On March 31, 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 the pricing of its previously announced underwritten public offering of 4,629,630 shares of its common stock and accompanying warrants to purchase up to 4,629,630 shares of common stock at a combined public offering price of $5.40 per share and accompanying warrant (Press release, Sellas Life Sciences, MAR 31, 2022, View Source [SID1234611335]). The warrants to purchase shares of common stock have an exercise price of $5.40 per share, are immediately exercisable and will expire five years from the date of issuance. All of the securities in the offering will be sold by SELLAS, with gross proceeds to SELLAS expected to be $25.0 million before deducting underwriting discounts and commissions and offering expenses. The offering is expected to close on April 5, 2022, subject to the satisfaction of customary closing conditions.

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SVB Leerink and Cantor are acting as joint book-running managers for the offering.

The public offering is being made pursuant to a shelf registration statement on Form S-3 (File No. 333-255318) that was previously filed with the Securities and Exchange Commission (the "SEC") on April 16, 2021 and declared effective on April 29, 2021. A final prospectus supplement and accompanying base prospectus relating to and describing the terms of the offering will be filed with the SEC and will be available on the SEC’s website located at View Source The offering is being made only by means of a prospectus and related prospectus supplement, copies of which may be obtained, when available, from SVB Securities LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected] or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, 4th Floor, New York, NY 10022, or by email at [email protected].

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

On March 31, 2022 Carina Biotech reported that we have submitted a pre-IND (Investigational New Drug) application to the US FDA (Food & Drug Administration) for our CAR-T therapy that targets a cancer stem cell antigen known as LGR5 (Press release, Carina Biotech, MAR 31, 2022, View Source [SID1234611333]).

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This represents a major step towards taking our CAR-T cell (CNA3103) into a Phase I/IIa clinical trial in patients with advanced colorectal (bowel) cancer later this year.

HIGHLIGHTS

A pre-IND package submission comes before a pre-IND meeting with the FDA, which will occur on 26 April
The next step will be the full IND application anticipated at the end of September 2022
Carina’s LGR5 CAR-T cells are targeted at LGR5, a cancer stem cell marker that is highly expressed on colorectal cancer (and other cancers)
Colorectal cancer is the deadliest cancer for Australians aged 25-34 and Australia’s second deadliest cancer overall
More than $US1 billion was earned by CAR-T therapy products in 2020*; and revenue of $US20.3 billion is forecast for 2028**
Carina Biotech CEO, Dr Deborah Rathjen said:

"Submitting our pre-IND package to the FDA is a milestone achievement for Carina as we transition from a discovery-stage pre-clinical company to a clinical-stage company, addressing unmet clinical needs in the treatment of solid cancers using our proprietary CAR-T technology to generate effective therapies that harness the power of the immune system."

Colorectal cancer is the third most commonly diagnosed cancer in Australia and in the United States, and the second leading cause of cancer deaths in Australia.

Metastatic colorectal cancer represents a significant unmet clinical need and has a large market potential. The therapeutics market is estimated at US$10.4 billion pa, growing at 4.6% pa.***

New CAR-T product approvals are anticipated to expand to an addressable patient population of 2 million within the next 10 years****, with solid tumours anticipated to account for more than 50% of CAR-T revenues by 2030*****.

About Carina’s LGR5 CAR-T cell
LGR5 is a cancer stem cell marker that is highly expressed on advanced colorectal cancer and some other cancers. In colorectal cancer patients, LGR5+ expression has been correlated with a particularly poor prognosis.

Cancer stem cells are a small sub-population of cells within a tumour with the ability to self-renew, differentiate into the many cell types of a tumour, initiate new tumours, and resist chemotherapy and radiotherapy (leading to relapses).

By targeting cancer stem cells, it is hoped that this therapy will reduce the tumour’s ability to generate new cancer cells, resulting in durable tumour suppression and preventing the relapses that are very common in patients with colorectal cancer.

Carina’s pre-clinical studies of the LGR5-targeted CAR-T cell have shown highly promising results with complete tumour regression and no tumour recurrence. They have also demonstrated impressive tumour access and prolonged CAR-T cell survival.

REFERENCES
*Yescarta and Kymriah market size estimates calculated from various publicly available sources. Estimates vary and different analyses may give different results. Estimated cost of goods US$58,200 (range $40,000-$106,000, 2018) with pricing outcomes/value based.
** Grandview Research, ‘T-cell therapy market size, share and trends analysis’, Feb 2021.
*** Calculated as the average of estimates published by Reportlinker, BCC Research and Nature Reviews Drug Discovery. Estimates vary and other analyses may give different results. Prevalence data is for US cases only.
**** Grandview Research, ‘T-cell therapy market size, share and trends analysis’, Feb 2021.
***** Polaris Market Research, ‘CAR-T cell therapy market share, size trends, industry analysis report’, June 2021.