On June 24, 2021 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported dose administration for the first patient in a Phase 1 U.S. clinical study for liver cancer treatment, with the company’s siRNA (small interfering RNA) drug candidate, STP705 (Press release, Sirnaomics, JUN 24, 2021, View Source [SID1234584342]). STP705 takes advantage of a dual-targeted inhibitory property and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expression.

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This Phase 1 trial is a multicenter, open-Label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of STP705, with an intratumoral administration. In this "basket study" of up to 50 subjects suffering from cholangiocarcinoma, hepatocellular carcinoma, or liver metastases from colorectal cancer, the patients with advanced/metastatic or surgically unresectable solid tumors and are refractory to standard therapy will be treated with STP705. This therapeutic regimen is designed to take advantage of a dual-targeted inhibitory property of siRNAs and polypeptide nanoparticle (PNP)-enhanced delivery to directly knock down both TGF-β1 and COX-2 gene expressions. Early pre-clinical and clinical studies using STP705 have shown an increase of active T cell infiltration into the tumor microenvironment. In addition, knocking down TGF-β1 and COX-2 gene expressions in animal fibrosis tissue can activate fibroblast apoptosis with significant antifibrotic efficacy.

"Advancing STP705 from skin cancer to liver cancer is a major milestone for Sirnaomics’ clinical programs, especially with a basket study design that consists of multiple tumor types. We are particularly interested in learning whether the mechanism of action validated in the skin cancer clinical study can be further verified in this liver cancer study," said Patrick Lu, Ph.D., founder, President and Chief Executive Officer of Sirnaomics. "We are expecting that the combination of anti-fibrotic effects and enhanced tumor immunity will provide a novel approach for the treatment of cholangiocarcinoma and hepatocellular carcinoma using our novel siRNA therapeutics. Sirnaomics is committed to advancing our polypeptide nanoparticle delivery system for innovative RNAi-based cancer therapy."

"Liver cancer is a devastating disease for patients with high mortality and high unmet medical need," stated Michael Molyneaux, MD, Chief Medical Officer of Sirnaomics. "The company is excited to announce first dosing, as we hope to gain important insight into the potential safety and efficacy of STP705 in this Phase 1 trial and build on the data from this study to expand into other oncology indications."

Sirnaomics expects to report initial clinical data from the Phase 1 trial in the second half of 2021. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT04676633

About Liver Cancer
Liver cancer is a global health problem, with liver neoplasms representing the second-most frequent cause of cancer-related death. There are many different types of liver cancers including hepatocellular carcinoma (HCC), cholangiocarcinoma, liver angiosarcoma, hepatoblastoma, and others. Additionally, the liver is a highly metastasis-permissive organ. It is the most frequently afflicted organ by metastasis and liver metastases are much more common than primary hepatic tumors. The distinctive biology of the liver renders it intrinsically susceptible to metastases. The true prevalence of liver metastasis is unknown, but between 30% and 70% of patients dying of cancer have liver metastases and most patients with liver metastases will die of their disease.

STP705 and Liver Cancer
Over expressions of TGF-β1 and COX-2 have been well-characterized as playing key regulatory roles in tumorigenesis. TGF-β is produced by different liver cells and is demonstrated to induce tumor cell migration and survival. TGF-β has been found to be overexpressed in metastatic HCC tissues. Overexpression of TGF-β is generally accepted to be associated with metastasis and poor prognosis. COX-2 is reported to be highly expressed in cancer stem cells and promotes cell migration in HCC cell lines. Additionally, inhibition of COX-2 suppresses cell migration and induces apoptosis. As such TGF-β1 and COX-2 are excellent therapeutic targets for treatment of liver cancer.

STP705 is composed of two siRNA oligonucleotides targeting TGF-β1 and COX-2 mRNA respectively and formulated in nanoparticles with a proprietary Histidine-Lysine Co-Polymer (HKP) peptide. Each individual siRNA has demonstrated the ability to inhibit the expression of their target mRNA and combining the two siRNAs produces a synergistic effect that diminishes pro-fibrogenic, pro-inflammatory, and pro-tumorigenic factors. Sirnaomics has completed several pre-clinical studies that demonstrate that inhibition of TGF-β1 and COX-2 and is expected to result in the inhibition of tumor growth and provide an alternative approach for the treatment of various liver cancers. Molecular analyses of the effects of administering the combination demonstrated that the inhibition of these targets had effects on downstream gene products associated with numerous oncology targets.

Additional immunohistochemistry and image analyses of the liver and tumor tissues demonstrated that animals treated with STP705 resulted in increased CD4+ and CD8+ T cell infiltration within the tumor microenvironment. Using STP705 for treatments of hepatocellular carcinoma and cholangiocarcinoma have been designated as Orphan Drug indications by U.S. FDA. STP705 has also been evaluated in a Phase 2a clinical trial for treatment of non-melanoma skin cancer.

On June 24, 2021 Bio-Techne Corporation (NASDAQ: TECH) and Catamaran Bio reported an expansion of their collaboration for the development of cell engineering and cell process technologies for use by Catamaran in the manufacturing of CAR-NK cell therapy products (Press release, Bio-Techne, JUN 24, 2021, View Source [SID1234584311]).

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The companies have now broadened the scope of their collaboration to include the development of novel cell expansion technologies for use in the manufacturing of CAR-NK cell therapy products. In addition, Catamaran has secured a broad worldwide license to Bio‑Techne’s rights related to the TcBuster transposon system for use in the research, clinical and commercial manufacturing of next generation allogeneic cell therapy products. Catamaran has integrated the TcBuster transposon system, a non-viral cell engineering technology that enables multiple gene editing and efficient delivery of large genetic payloads, into its TAILWIND Platform for CAR-NK cell therapies.

The initial collaboration between Catamaran and Bio-Techne, which began in 2020, has been focused on optimizing the application of the TcBuster transposon system to CAR-NK cell engineering. The TcBuster transposon system was developed at B-MoGen Biotechnologies by a team that included Catamaran’s scientific co-founder, Branden Moriarty, PhD, Assistant Professor in the Department of Pediatrics, Division of Hematology/Oncology at the University of Minnesota. Bio-Techne acquired B-MoGen Biotechnologies in 2019.

"Our agreements with Catamaran open the path for Bio-Techne’s cutting-edge cell engineering and process technologies to deliver gene-modified CAR-NK cell therapies for cancer," said Dave Eansor, President of Bio-Techne’s Protein Sciences Segment. "We are delighted to expand our relationship with Catamaran and increase our impact in the cell therapy space."

"We have established a successful track record of collaborating with Bio-Techne to optimize technologies for use in CAR-NK cell engineering and manufacturing. This collaboration and license exemplify our strategy to access technologies that provide important advantages in the cell therapy manufacturing process, as we position Catamaran as a leader in developing off-the-shelf CAR-NK cell therapies for solid tumors," said Alvin Shih, MD, President and Chief Executive Officer of Catamaran Bio.

Through the collaboration, the Catamaran and Bio-Techne teams are focused on developing and enhancing technologies for scalable and robust manufacturing of allogeneic CAR-NK cell therapies. Bio-Techne will contribute innovative cell expansion technologies and both companies will contribute know-how to enable large-scale production of functional CAR-NK cells.

"We are excited to be making advances with innovative technologies that enable Catamaran to achieve scalable and robust manufacturing processes for our CAR-NK cell therapies. We are committed to incorporating transformative technologies into our TAILWIND Platform as we advance our product candidates toward the clinic and enable allogeneic CAR-NK cell therapies to reach their therapeutic potential," said Vipin Suri, PhD, Chief Scientific Officer of Catamaran Bio.

On June 24, 2021 Starpharma (ASX: SPL, OTCQX: SPHRY) reported that a presentation by Dr Jackie Fairley, CEO, reported that it will be broadcast on Thursday 24 June 2021 (US ET) as part of OTCQX’s Virtual Life Sciences Investor Forum (Press release, Starpharma, JUN 24, 2021, View Source;mc_eid=bf52dd3418 [SID1234584327]). The Life Sciences Investor Forum is a leading investor conference that is attended by tens of thousands of investors, primarily US-based retail investors, as well as advisors.

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Details of the forum are found via this link: Virtual Life Sciences Investor Forum. Starpharma’s pre-recorded presentation features a company overview, including the latest updates on the VIRALEZE Antiviral Nasal Spray which has shown potent antiviral activity against multiple variants of coronavirus/SARS-CoV-2 in laboratory studies, and has been registered in Europe (launched) and India. The presentation will also include an overview of Starpharma’s DEP clinical-stage and preclinical assets, and corporate partnerships for its DEP drug delivery platform, including with Merck & Co., Inc (MSD) and AstraZeneca, as well as its VivaGel products, which are approved in more than 45 countries. The presentation is attached and also available on Starpharma’s website.

On June 24, 2021 Centene Corporation (NYSE: CNC) ("Centene" or the "Company") reported that it has commenced an underwritten public offering to sell $1,800,000,000 of senior notes due 2028 (the "Notes"), subject to market and other conditions (Press release, Centene , JUN 24, 2021, View Source [SID1234584343]).

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Centene intends to use the net proceeds from the offering of the Notes to finance a portion of the cash consideration payable in connection with Centene’s previously announced acquisition of Magellan Health Inc. ("Magellan Health" and such proposed acquisition, the "Magellan Acquisition") and to pay related fees and expenses. The closing of the offering is not conditioned on the closing of the Magellan Acquisition. If the Magellan Acquisition is not completed, Centene expects to use the net proceeds of the offering for debt repayment and general corporate purposes.

J.P. Morgan, Barclays, BofA Securities, Truist Securities and Wells Fargo Securities are acting as joint book-running managers for the offering of the Notes.

This offering is being made pursuant to an effective shelf registration statement and prospectus and a related preliminary prospectus supplement filed by the Company with the Securities and Exchange Commission (the "SEC"). Before you invest, you should read the prospectus and the related preliminary prospectus supplement, the registration statement and other documents that Centene has filed with the SEC for more complete information about Centene and this offering.

Copies of the prospectus supplement and related prospectuses for this offering can be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by calling +1 (866) 803-9204; from Barclays Capital Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected], or by calling (888) 603-5847; from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, NC 28255-0001, Attn: Prospectus Department or by email at [email protected]; from Truist Securities by email at [email protected]; and from Wells Fargo Securities, LLC, 550 S. Tryon Street, 5th Floor, Charlotte, North Carolina 28202, Attention: Leveraged Syndicate.

This press release is neither an offer to purchase nor a solicitation of an offer to buy any securities, including the Notes. There shall not be any sale of the securities described herein in any state or other 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 other jurisdiction.

On June 24, 2021, Athersys, Inc. (the "Company," "we," "us" or "our") reported that it entered into a common stock purchase agreement (the "Purchase Agreement") with Aspire Capital Fund, LLC ("Aspire Capital"), which provides that, upon the terms and subject to the conditions and limitations set forth therein, Aspire Capital is committed to purchase up to an aggregate of $100 million of shares of the Company’s common stock over the 36-month term of the Purchase Agreement (Filing, 8-K, Athersys, JUN 24, 2021, View Source [SID1234584361]).

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Concurrently with entering into the Purchase Agreement, the Company also entered into a registration rights agreement with Aspire Capital (the "Registration Rights Agreement"), pursuant to which the Company agreed to file one or more registration statements, as permissible and necessary to register under the Securities Act of 1933, as amended (the "Securities Act"), the sale of the shares of the Company’s common stock that may be issued to Aspire Capital under the Purchase Agreement.

The Purchase Agreement provides that the number of shares of our common stock that may be sold pursuant to the Purchase Agreement shall be limited to 40,000,000 shares.

Pursuant to the Purchase Agreement and the Registration Rights Agreement, we intend to register under the Securities Act the sale of 40,000,000 shares of our common stock that we may issue to Aspire Capital after the registration statement referred to above (the "Registration Statement") is declared effective under the Securities Act.

After the U.S. Securities and Exchange Commission (the "SEC") has declared the Registration Statement effective, on any business day on which the closing sale price of the Company’s common stock equals or exceeds $1.00 per share, we have the right, in our sole discretion, to present Aspire Capital with a purchase notice (each, a "Purchase Notice"), directing Aspire Capital (as principal) to purchase up to 200,000 shares of our common stock per trading day, provided that the aggregate price of such purchase shall not exceed $500,000 per trading day, up to $100 million of our common stock in the aggregate. The purchase price per share pursuant to such Purchase Notice (the "Purchase Price") is the lower of (i) the lowest sale price for the Company’s common stock on the date of sale or (ii) the arithmetic average of the three lowest closing sale prices for the Company’s common stock during the ten consecutive business days ending on the business day immediately preceding the purchase date of those securities. The applicable Purchase Price will be determined prior to delivery of any Purchase Notice.

In addition, on any date on which we submit a Purchase Notice to Aspire Capital in an amount of at least 100,000 shares, we also have the right, in our sole discretion, to present Aspire Capital with a volume-weighted average price purchase notice (each, a "VWAP Purchase Notice") directing Aspire Capital to purchase an amount of the Company’s common stock equal to a percentage (not to exceed 30%) of the aggregate shares of common stock traded on the NASDAQ Capital Market on the next business day (the "VWAP Purchase Date"), subject to a maximum number of shares determined by the Company (the "VWAP Purchase Share Volume Maximum"). The purchase price per share pursuant to such VWAP Purchase Notice (the "VWAP Purchase Price") shall be the lower of (i) the closing sale price on the date of sale and (ii) 95% of the volume weighted average price for the Company’s common stock traded on the NASDAQ Capital Market on (a) the VWAP Purchase Date if the aggregate shares to be purchased on that date does not exceeded the VWAP Purchase Share Volume Maximum and the sale price of our common stock has not fallen below the price set by us in the VWAP Purchase Notice (the "VWAP Minimum Price Threshold") (to be appropriately adjusted for any reorganization, recapitalization, non-cash dividend stock split, reverse stock split or other similar transaction) or (b) the portion of such business day until such time as the aggregate shares to be purchased will equal the VWAP Purchase Share Volume Maximum. Further, if the sale price of our common stock falls on the VWAP Purchase Date below the greater of (i) 90% of the closing price of our common stock on the business day immediately preceding the VWAP Purchase Date or (ii) the VWAP Minimum Price Threshold, the VWAP Purchase Price will be determined using the percentage in the VWAP Purchase Notice of the total shares traded for such portion of the VWAP Purchase Date prior to the time that the sale price of our common stock fell below the VWAP Minimum Price Threshold and the volume weighted average price of our common stock sold during such portion of the VWAP Purchase Date prior to the time that the sale price of our common stock fell below the VWAP Minimum Price Threshold.

The floor price and the respective prices and share numbers in the preceding paragraphs shall be appropriately adjusted for any reorganization, recapitalization, stock dividend, stock split, reverse stock split or other similar transaction. Additionally, the Purchase Agreement provides that the Company and Aspire Capital shall not effect any sales under the Purchase Agreement if such shares proposed to be issued and sold, when aggregated with all other shares of the Company’s common stock that Aspire Capital and its affiliates beneficially own, would result in Aspire Capital and its affiliates beneficially owning more than 19.99% of the Company’s then issued and outstanding common stock.

There are no trading volume requirements or restrictions under the Purchase Agreement, and we will control the timing and amount of any sales of our common stock to Aspire Capital. Aspire Capital has no right to require any sales by us, but is obligated to make purchases from us as we direct in accordance with the Purchase Agreement. The Company may deliver multiple Purchase Notices and VWAP Purchase Notices to Aspire Capital from time to time during the term of the Purchase Agreement, so long as the most recent purchase has been completed. There are no limitations on use of proceeds, financial or business covenants, restrictions on future fundings, rights of first refusal, participation rights, penalties or liquidated damages in the Purchase Agreement. The Purchase Agreement may be terminated by us at any time, at our discretion, without any penalty or cost to us. Also, Aspire Capital has agreed that neither it nor any of its agents, representatives and affiliates shall engage in any direct or indirect short-selling or hedging, which establishes a net short position with respect to our common stock during any time prior to the termination of the Purchase Agreement.

The Purchase Agreement provides for customary events of default, upon the occurrence of which Aspire Capital may terminate the Purchase Agreement. Such events of default include, without limitation:

the lapse, or unavailability to Aspire Capital for the sale of shares of the Company’s common stock, of any registration statement that is required to be maintained effective pursuant to the terms of the Registration Rights Agreement, subject to specified cure periods;

the suspension from trading or failure of the Company’s common stock to be listed on a Principal Market (as defined in the Purchase Agreement) for a period of three consecutive business days;

the delisting of the Company’s common stock from the Principal Market, provided the Company’s common stock is not immediately thereafter trading on the New York Stock Exchange, the NYSE American, the NASDAQ Global Select Market, the NASDAQ Global Market or the NASDAQ Capital Market;

the failure for any reason by the Company’s transfer agent to issue shares to Aspire Capital within five business days after the applicable purchase date that Aspire Capital is entitled to receive such shares;

if any proceeding against the Company is commenced pursuant to or within the meaning of any bankruptcy law;

if at any time the number of shares sold pursuant to the Purchase Agreement exceeds 40,000,000 shares, if applicable, unless and until stockholder approval is obtained; and

any breach by the Company of the representations, warranties, covenants or other term or condition contained in the Purchase Agreement or any related agreements that would reasonably be expected to have a material adverse effect, except, in the case of a breach of a covenant which is reasonably curable, only if such breach continues for a period of at least five business days.

The foregoing is a summary description of certain terms of the Purchase Agreement and the Registration Rights Agreement. For a full description of all terms, please refer to copies of the Purchase Agreement and the Registration Rights Agreement that are filed herewith as Exhibits 10.1 and 10.2, respectively, to this Current Report on Form 8-K and are incorporated herein by reference. All readers are encouraged to read the entire text of the Purchase Agreement and the Registration Rights Agreement.

The issuance of all shares of common stock that may be issued from time to time to Aspire Capital under the Purchase Agreement is exempt from registration under the Securities Act, pursuant to the exemption for transactions by an issuer not involving any public offering under Section 4(a)(2) of the Securities Act and Rule 506 of Regulation D promulgated thereunder.