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.

On June 24, 2021 EQRx, a company committed to developing and delivering important new medicines to patients at radically lower prices, and Exscientia, an AI-driven pharmatech company with a mission to radically improve how drugs are discovered, reported a strategic research and development collaboration agreement (Press release, EQRx, JUN 24, 2021, View Source [SID1234584312]). The collaboration will leverage the AI capabilities of Exscientia to accelerate the discovery of small molecule therapeutic drug candidates in multiple therapeutic areas, including oncology and immunology, further expanding the breadth of EQRx’s pipeline of novel therapies.

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This innovative collaboration is focused on creating significant improvements in the traditional drug discovery and development processes by improving the probability of success through each company’s unique capabilities to accelerate the delivery of innovative new medicines—from discovery to commercialization.

Under the terms of the agreement, the strengths of both companies will be leveraged throughout the drug development process. Exscientia will lead the discovery phase through to Investigational New Drug application (IND) filing, while EQRx will be responsible for clinical development, regulatory and commercialization efforts. EQRx and Exscientia will equally share in the discovery, development and commercialization costs.

"Exscientia is a leader in AI-driven drug discovery, and of particular note, has now brought multiple AI-engineered drug candidates to clinical trials. We believe that our aligned focus on efficiency and quality sets a truly unique course to bring the next generation of innovative medicines to patients faster and at a fraction of the cost," said Alexis Borisy, chairman and chief executive officer of EQRx. "This is a significant step in building EQRx’s robust, sustainable and industry-leading pipeline of important new medicines and substantially accelerates our early-stage research capabilities."

"We are impatient for patients. EQRx and Exscientia are partners who are equally focused on re-engineering the way we create and distribute drugs for better outcomes for more patients. This exciting new collaboration brings together technologies through a new model that has the potential to truly disrupt how we think about efficiently creating innovative new medicines for all patients," said Andrew Hopkins, chief executive officer of Exscientia. "Together with the team at EQRx we look forward to building a successful partnership, to enable more patients to access better drugs, faster."

On June 24, 2021 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical company with a robust pipeline of novel investigational therapeutics built on protein dysregulation expertise, reported that Bristol Myers Squibb exercised its option under the global neuroscience research and development collaboration to enter into an exclusive U.S. license for PRX005 and will pay Prothena $80 million (Press release, Prothena, JUN 24, 2021, View Source [SID1234584328]). PRX005 is designed to be a best-in-class anti-tau antibody by specifically targeting an area within the microtubule binding region (MTBR) for the potential treatment of Alzheimer’s disease (AD). Phase 1 study with PRX005 has initiated.

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"Our continued collaboration with Bristol Myers Squibb on PRX005 allows us to further leverage our combined expertise to accelerate the development of therapies with the potential to transform the lives of those affected by neurodegeneration," said Gene Kinney, PhD, President and Chief Executive Officer of Prothena. "Mounting scientific evidence suggests the MTBR of tau is most closely associated with the pathogenic spread of tau. The presence of MTBR fragments in cerebrospinal fluid have also been shown to correlate with dementia stages in Alzheimer’s disease to a higher degree than fragments of other tau regions. These recent biological understandings support the further development of PRX005, which uniquely targets a key region within the MTBR of the tau protein. In our studies, we have found that targeting specific regions within the MTBR reduce pathogenic tau uptake into neurons, an attribute that was not achievable with antibodies targeting other regions of tau."

"We are pleased that our collaboration with Prothena has successfully identified and developed PRX005, a novel, differentiated anti-tau antibody that we believe has the potential to provide a meaningful disease modifying treatment option for the millions of patients that suffer from Alzheimer’s disease," said Richard Hargreaves, Senior Vice President and Head of Bristol Myers Squibb’s Neuroscience Thematic Research Center. "We look forward to our continued partnership with Prothena."

Tau is a microtubule associated protein, which aggregates and hyper-phospohrylates in the brains of individuals with AD to form pathological neurofibrillary tangles. Tau tangles, along with amyloid beta plaques represent the pathological hallmarks of AD. The presence of tau pathology strongly correlates with neurodegeneration and cognitive impairment in AD and its pattern of progression throughout the brain suggests that tau pathology spreads through anatomically connected pathways via cell-to-cell transmission, a hypothesis supported by multiple preclinical studies. This propagation of pathology is thought to be mediated by tau "seeds" containing the MTBR of tau. PRX005 has demonstrated superior ability to bind, intercept and block cellular internalization of pathogenic tau, and mitigate downstream neurotoxicity compared to other anti-tau antibodies in multiple preclinical studies.

About the Global Neuroscience Research and Development Collaboration

This global neuroscience research and development collaboration is focused on three proteins implicated in the pathogenesis of several neurodegenerative diseases, including tau, TDP-43 and an undisclosed target. PRX005 is designed to be a best-in-class anti-tau, MTBR-specific antibody for the potential treatment of Alzheimer’s disease and is the first program to advance to the clinic from this collaboration, where the Phase 1 study has initiated. With this payment, Prothena will have received a total of $230 million pursuant to the collaboration, and is eligible to receive up to an additional $160 million for U.S. rights, up to $165 million for global rights, and up to $1.7 billion for regulatory and commercial milestone payments for a total of up to $2.2 billion plus potential tiered commercial sales royalties across multiple programs.

About PRX005 for Alzheimer’s Disease

PRX005 is designed to be a best-in-class anti-tau antibody that specifically targets a key region within the microtubule binding region (MTBR), which has been shown in preclinical studies to be involved in the pathological spread of tau. Neurofibrillary tangles composed of misfolded tau proteins, along with amyloid beta plaques, are pathological hallmarks of Alzheimer’s disease (AD). Cell-to-cell transmission of pathogenic extracellular tau and the accumulation of pathogenic tau also correlate with the progression of symptomatology and clinical decline in patients with AD. Recent publications suggest that during the course of AD progression, tau appears to spread throughout the brain via synaptically-connected pathways; this propagation of pathology is thought to be mediated by tau "seeds" containing the MTBR of tau. Additionally, it has been recently reported that the presence of MTBR fragments in cerebrospinal fluid correlate with dementia stages in AD to a higher degree than fragments of other tau regions. In preclinical research, antibodies targeting this region of tau were superior in blocking tau uptake and neurotoxicity, which has been associated with efficacy in AD animal models. In these preclinical models, PRX005 demonstrated significant inhibition of cell-to-cell transmission and neuronal internalization in vitro and in vivo and slowed pathological progression in a tau transgenic mouse model.

About Alzheimer’s Disease

Alzheimer’s disease is a type of dementia that can cause increasingly serious symptoms, including confusion, disorientation, mood and behavioral changes, difficulty speaking, swallowing, and walking. Approximately 6.2 million Americans age 65 and older are currently estimated to be living with Alzheimer’s disease, making it the most common neurodegenerative disorder. It is also the sixth leading cause of death among adults in the United States. There is an urgent need for therapies that slow the progression and ultimately prevent Alzheimer’s disease to address this global healthcare crisis. Prothena’s Alzheimer’s disease portfolio spans next generation antibody immunotherapy, small molecule and vaccine approaches, geared toward building upon first generation treatments to advance the treatment paradigm.

On June 24, 2021 Shenzhen Chipscreen Biosciences’ licensing partner, HUYABIO International (HUYABIO), reported the regulatory approval for Tucidinostat (also known as Chidamide, Epidaza , HBI-8000) monotherapy of relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATL) by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) (Press release, Shenzhen Chipscreen Biosciences, JUN 24, 2021, View Source;huyabio-international-receives-regulatory-approval-for-chidamide-monotherapy-of-adult-t-cell-leukemialymphoma-in-japan-301319258.html [SID1234584344]).

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"Relapsed and/or refractory ATLL carries a grim prognosis with limited treatment options. Data from the registration study of Chidamide has demonstrated meaningful disease response despite the advanced stage of disease, and acceptable safety profile, to address an important unmet medical need in this patient population", said Dr. Atae Utsunomiya, honorary hospital director of Imamura General hospital in Japan.

The drug was approved based on data from a Phase 2b study that involved 23 patients with aggressive ATL in Japan. These patients, having few effective treatment options, all had advanced disease either refractory to or relapsed after receiving mogamulizumab. Chidamide 40mg orally administered twice weekly resulted in disease response in a clinically meaningful proportion of patients with an acceptable safety profile.

Dr. Lu Xianping, Chairman and President of Chipscreen said, "this is an exciting news and important milestone for our licensing partner HUYABIO International and we wish them continue success in the global development of Chidamide for several other indications".

About Chidamide (Tucidinostat as INN also known as Epidaza , HBI-8000)

Chidamide is a first-in-class/best-in-class innovative medicine targeting selectively histone deacetylases (HDAC) 1, 2, 3 and 10, which was discovered and developed originally by Shenzhen Chipscreen Biosciences in China. It has unique epigenetic immunomodulatory activities approved and launched in Chinese market for the treatment of malignant T cell lymphoma at 2014 and metastatic breast cancer at 2019. It is currently at several late stage clinic studies for several other indications in China. The product’s ex-China rights were licensed out from Chipscreen to HUYABIO at 2006. Later on, HUYABIO partnered with Meiji Seika for Japanese market.

On June 24, 2021 Monte Rosa Therapeutics reported that it is capping off a fundraising spree with a $222.3 million IPO to get two of its "molecular glue" treatments into the clinic and advance its other discovery-stage programs (Press release, Monte Rosa Therapeutics, JUN 24, 2021, View Source [SID1234584378]).

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The company raised $96 million in September 2020 to develop its drug discovery platform and expand its pipeline into diseases beyond cancer. It followed up with another $95 million six months later, ending the first quarter of 2021 with $168.4 million, according to a securities filing. Of course, drug development is an expensive business, and Monte Rosa filed in early June to raise up to $100 million in its IPO.

Despite being a preclinical biotech with much to prove, it bumped that IPO goal up to $213 million earlier this week, eventually collecting $222.3 million by offering 20% more shares than originally planned. But seeing a biotech go public without any human data isn’t unusual these days; even before the COVID-19 pandemic spurred interest and investment in the sector, companies had been hitting Wall Street at increasingly earlier stages of development.

RELATED: Monte Rosa snags $95M to speed lead ‘molecular glue’ treatment into the clinic

Molecular glues are small molecules designed to treat disease by commandeering the body’s own protein degrading process. As their name suggests, they work by sticking proteins to each other.

Monte Rosa earmarked about $47 million to $57 million for a cancer treatment that targets GSPT1, which plays a role in cancers driven by the Myc family of transcription factors. The cash should get it through a phase 1/2 study.

Beyond GSPT1, Monte Rosa will use between $120 million and $130 million to get a second program into phase 1, a third program to an IND filing and a fourth to IND-enabling studies, according to the filing. Another $65 million to $75 million will bankroll the development of its drug discovery platform.

"[Molecular glues] work by allosterically changing the receptor surface of E3 ligases to attract a protein target," said Monte Rosa CEO Markus Warmuth, M.D., referring to enzymes that tag proteins with ubiquitin for degradation by a protein complex called a proteasome, in a previous interview. "We have a singular focus on finding these molecules that reshape the surface of an E3 ligase and thereby attract otherwise undruggable targets."

RELATED: Sana snags $587.5M IPO to catapult cell therapies into the clinic

The best-known molecular glue medicines are thalidomide and its successor molecule lenalidomide—aka Bristol Myers Squibb’s blood cancer drug Revlimid—which both reshape an E3 ligase receptor called cereblon. However, this class of drugs hasn’t been hunted in a systematic way in the past, which is exactly what Monte Rosa’s technology allows it to do.

Monte Rosa isn’t alone in the protein degradation field, but it believes molecular glues can go where other approaches cannot. Other players are working on the hypothesis that eliminating disease driving proteins is a better approach than inhibiting them. They’re "redrugging the druggable," Warmuth said, developing degraders for targets that can be inhibited by traditional drugs.

Arvinas, for example, is developing drugs called proteolysis targeting chimeras, or PROTACs, to degrade the androgen and estrogen receptors, which are major drivers of prostate cancer and breast cancer, respectively. And Kymera Therapeutics is working on degraders of scaffolding kinase IRAK4 and transcription factor STAT3, both of which play a role in cancer.

Monte Rosa wants to go after targets like GSPT1 that haven’t been accessible because drug developers didn’t have the technology to handle them.