MNK1

SINGAPORE and BETHESDA, Md., Nov. 15, 2022 (GLOBE NEWSWIRE) -- AUM Biosciences Pte. Ltd. (“AUM”), a clinical-stage biotechnology company, advancing a clinical stage candidate and a broader pipeline designed to deploy multi-faceted inhibition strategies to reverse cancer resistance, today announced it has received Human Research Ethics Committee (“HREC”) approval to commence a Phase II clinical trial of its selective translation inhibitor AUM001 in Australia. Ethics approval is confirmation that AUM has completed all the necessary pre-clinical safety and efficacy testing of AUM001 required to commence its Phase II clinical trial in Australia. “Ethics approval in Australia provides further validation of the study design recently approved under an IND by the U.S. FDA,” said Vishal Doshi, CEO of AUM. “We are proud of our ability to continue to make progress in the development of AUM001, having obtained authorization for our U.S. IND in May. We are very much looking forward to commencing dosing in Part 1 of the Phase II trial before the end of 2022,” added Doshi. This trial is a Phase II open label, dose-finding run-in and cohort expansion study to evaluate the safety, tolerability and effectiveness of AUM001 in combination with pembrolizumab or irinotecan for the treatment of metastatic colorectal cancer. It will be conducted in two parts: (1) dose escalation run-in to identify the Maximum Tolerable Dose and the Recommended Phase II Dose (“RP2D”) of AUM001 to be administered orally as monotherapy and in combination with pembrolizumab or irinotecan, and (2) a cohort expansion at the RP2D of AUM001 in combination with pembrolizumab or irinotecan in patients with locally advanced or metastatic colorectal cancer to evaluate the clinical activity and safety of AUM001. Part 1 of the global Phase II trial will be conducted under Australia’s Clinical Trials Notification Scheme meaning AUM will notify the Therapeutic Goods Administration of HREC approval and complete local site initiation activities. AUM plans to open six clinical sites for Part 1 in Australia. In May 2022, AUM received authorization from the U.S. Food and Drug Administration (“FDA”) of its Investigational New Drug (“IND”) application for the clinical trial evaluating AUM001 to treat metastatic colorectal cancer. Study details can also be found on under study ID: NCT05462236. The global Phase 2 trial is being conducted in collaboration with MSD, a tradename of Merck & Co., Inc., pursuant to a clinical trial collaboration and supply agreement. About AUM001 AUM001 is a highly selective translation inhibitor. In vitro, it was observed to selectively inhibit mitogen-activated protein kinase (MAPK) – interacting protein kinase (MNK) types 1/2 and is expected to thereby block phosphorylation of eIF4E, and in turn, interfere with CAP mediated RNA translation, thereby impairing growth signals involved in cancer development, progression, and resistance to therapies. MNK is important in tumor microenvironment regulation, shifting the balance towards tumor inhibition. Moreover, inhibition of MNK kinases decreases the production of the pro-inflammatory cytokines like TNFα and IL-6, suggesting that MNK kinases and their substrates (eIF4E, hnRNP A1, Spry1/2) play a pivotal role in regulating the innate and adaptive immune compartment. This has the potential to turn “cold” tumors “hot”, increasing the proportion of tumors susceptible to immunotherapies. AUM001 demonstrated encouraging safety, tolerability, and target engagement as a monotherapy in two phase 1 clinical trials. On October 20, 2022, AUM and Mountain Crest Acquisition Corp. V (Nasdaq: MCAG) (“Mountain Crest”), a publicly traded special purpose acquisition company formed in Delaware, whose management team has an impressive pedigree of successful SPAC transactions, announced that they have entered into a definitive business combination agreement (the “Agreement”). Upon closing of the transaction, the combined company will operate under a holding entity, AUM Biosciences Limited, a Cayman Islands exempted company (“Holdco”), and intends to trade on the Nasdaq Stock Market under the ticker symbol AUMB. About AUM Biosciences AUM is a global clinical-stage oncology company focused on advancing a pipeline of precision oncology therapeutics designed to deploy multi-faceted inhibition strategies to reverse cancer resistance. AUM is advancing a broad portfolio of precision oncology therapeutics. AUM001 is a selective and synergistic MNK inhibitor as shown in current studies and expected to begin Phase 2 enrollment in the fourth quarter 2022. AUM601 is a promising therapy for Tropomyosin Receptor Kinase (TRK) fusions and mutations within the kinase domain and is on track to enter Phase 2 planning. AUM302 is a potentially first-in-class macrocyclic oral kinase inhibitor rationally designed small molecule to uniquely combine pan-PIM kinase, pan-PI3K and mTOR inhibition in a single agent. Comprised of pharma industry veterans with decades of research and development experience, the AUM leadership has an extensive track record of selecting distinctive early-stage assets, successfully exiting virtual biotech models, and has contributed to over 50 INDs and over 150 oncology clinical trials, and development of several currently marketed oncology treatments with annual peak sales up to $3 billion. About Mountain Crest Mountain Crest Acquisition Corp. V (Nasdaq: MCAG) is a blank check company formed for the purpose of effecting a merger, share exchange, asset acquisition, share purchase, reorganization or similar business combination with one or more businesses. Non-Solicitation This press release shall not constitute a solicitation of a proxy, consent, or authorization with respect to any securities or in respect of the proposed business combination. This press release shall also not constitute an offer to sell or the solicitation of an offer to buy any securities, nor shall there be any sale of securities in any states or jurisdictions in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdiction. No offering of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the Securities Act of 1933, as amended, or an exemption therefrom. Important Information About the Proposed Business Combination and Where to Find It In connection with the proposed business combination, AUM, Mountain Crest and/or a successor entity of the transaction intends to materials with the SEC, including a registration statement on Form F-4 containing a proxy statement/prospectus (the “Registration Statement”). The Registration Statement will include a proxy statement/prospectus to be distributed to holders of Mountain Crest’s common stock in connection with Mountain Crest’s solicitation of proxies for the vote by Mountain Crest’s stockholders with respect to the proposed transaction and other matters as described in the Registration Statement, as well as the prospectus relating to the offer of securities to be issued to AUM’s stockholders in connection with the proposed business combination. After the Registration Statement has been filed and declared effective, Mountain Crest will mail a definitive proxy statement, when available, to its stockholders. Copies of these documents may be obtained free of charge at the SEC's website at Stockholders of Mountain Crest are urged to read the Registration Statement and the other relevant materials when they become available before making any voting decision with respect to the proposed business combination because they will contain important information. The information contained on, or that may be accessed through, the website referenced in this press release is not incorporated by reference into, and is not a part of, this press release. Participants in the Solicitation Mountain Crest and its directors and executive officers may be deemed participants in the solicitation of proxies from Mountain Crest’s stockholders with respect to the business combination. A list of the names of those directors and executive officers and a description of their interests in Mountain Crest will be included in the Registration Statement for the proposed business combination and be available at Additional information regarding the interests of such participants will be contained in the Registration Statement for the proposed business combination when available. Information about Mountain Crest’s directors and executive officers and their ownership of Mountain Crest common stock is set forth in Mountain Crest’s Annual Report on Form 10-K for the fiscal year ended December 31, 2021, as modified or supplemented by any Form 3 or Form 4 filed with the SEC since the date of such filing. Other information regarding the interests of the participants in the proxy solicitation will be included in the Registration Statement pertaining to the proposed business combination when it becomes available. These documents can be obtained free of charge from the sources indicated above. AUM and its directors and executive officers may also be deemed to be participants in the solicitation of proxies from the stockholders of Mountain Crest in connection with the proposed business combination. A list of the names of such directors and executive officers and information regarding their interests in the proposed business combination will be included in the Registration Statement for the proposed business combination. Forward-Looking Statements This press release includes “forward-looking statements” within the meaning of the “safe harbor” provisions of the United States Private Securities Litigation Reform Act of 1995. Mountain Crest’s and AUM’s actual results may differ from their expectations, estimates, and projections and, consequently, you should not rely on these forward-looking statements as predictions of future events. Words such as “expect,” “estimate,” “project,” “budget,” “forecast,” “anticipate,” “intend,” “plan,” “may,” “will,” “could,” “should,” “believes,” “predicts,” “potential,” “continue,” and similar expressions (or the negative versions of such words or expressions) are intended to identify such forward-looking statements. These forward-looking statements include, without limitation, Mountain Crest’s and AUM’s expectations with respect to future performance and anticipated financial impacts of the proposed business combination, the satisfaction of the closing conditions to the proposed business combination, and the timing of the completion of the proposed business combination. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from those discussed in the forward-looking statements. Most of these factors are outside Mountain Crest’s and AUM’s control and are difficult to predict. Factors that may cause such differences include, but are not limited to: (1) the occurrence of any event, change, or other circumstances that could give rise to the termination of the Agreement; (2) the outcome of any legal proceedings that may be instituted against Mountain Crest and AUM following the announcement of the Agreement and the transactions contemplated therein; (3) the inability to complete the proposed business combination, including due to failure to obtain approval of the stockholders of Mountain Crest and AUM, certain regulatory approvals, or satisfy other conditions to closing in the Agreement; (4) the occurrence of any event, change, or other circumstance that could give rise to the termination of the Agreement or could otherwise cause the transaction to fail to close; (5) the impact of the COVID-19 pandemic on AUM’s business and/or the ability of the parties to complete the proposed business combination; (6) the inability to obtain the listing of Holdco’s ordinary shares on Nasdaq following the proposed business combination; (7) the risk that the proposed business combination disrupts current plans and operations as a result of the announcement and consummation of the proposed business combination; (8) the ability to recognize the anticipated benefits of the proposed business combination, which may be affected by, among other things, competition, the ability of AUM to grow and manage growth profitably, and retain its key employees; (9) costs related to the proposed business combination; (10) changes in applicable laws or regulations; (11) the possibility that Mountain Crest or AUM may be adversely affected by other economic, business, and/or competitive factors; (12) risks relating to the uncertainty of the projected financial information with respect to AUM; (13) risks related to the organic and inorganic growth of AUM’s business and the timing of expected business milestones; (14) the amount of redemption requests made by Mountain Crest’s stockholders; and (15) other risks and uncertainties indicated from time to time in the final prospectus of Mountain Crest for its initial public offering and the Registration Statement relating to the proposed business combination, including those under “Risk Factors” therein, and in Mountain Crest’s other filings with the SEC. Mountain Crest cautions that the foregoing list of factors is not exclusive. Mountain Crest and AUM caution readers not to place undue reliance upon any forward-looking statements, which speak only as of the date made. Mountain Crest and AUM do not undertake or accept any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements to reflect any change in their expectations or any change in events, conditions, or circumstances on which any such statement is based. Investors: ICR Westwicke Stephanie Carrington T: (646) 277-1282 stephanie.carrington@westwicke.com Media: FINN Partners Glenn Silver T: (973) 818-8198 glenn.silver@finnpartners.com SPAG/FINN Verlynn Heng +65-91861225 verlynn.heng@spag.asia

In Ratatouille , Remy the rat controls a young cook from his chef’s hat, directing his every move in the restaurant kitchen and helping him make food. Well, messenger RNAs have a Remy too. Cap-binding proteins that bind to one end of RNA sequences direct how they are spliced and translated into proteins. In particular, the protein eIF4E binds to mRNA caps and guides translation (the eIF stands for eukaryotic translation initiation factor). That’s the protein that PIC Therapeutics is targeting in hopes of treating breast cancer — and now it has $35 million in funding to get that program into the clinic. The round was led by OrbiMed, followed by Lumira Ventures and Harrington Discovery Institute. The biotech’s two seed investors — Advent Life Sciences and Belinda Termeer, the widow of Genzyme CEO Henri Termeer — also joined in. Gerhard Wagner PIC has been around for a bit. It was spun out in 2016 from the lab of Harvard physicist Gerhard Wagner, but made some major moves in 2020. That April, it completed its seed round for $5 million, after which it lured Kathy Bowdish from Sanofi. During her tenure at the French pharma, Bowdish led the creation of Sanofi Sunrise, Sanofi’s early-stage venture arm. Bowdish told Endpoints News that PIC’s focus on mRNA translation took her back to her graduate school research, in which she studied yeast transcription. PIC’s small molecules modulate eIF4E indirectly, but instead of blocking translation, Bowdish said they upregulate genes for cell death and downregulate oncogene expression. And by targeting translation, PIC is aiming at “not a specific point in a single signaling pathway, but a fundamental mechanism that works across a number of cancer-driving oncogenes,” Bowdish said. Bowdish emphasized that inducing cell death was important. “Rather than having senescent cells still sitting there, potentially generating resistance mechanisms, it looks to us like we are actually rapidly inducing apoptosis in tumor cells,” she said. PIC’s first goal is metastatic and drug-resistant breast cancer. After getting first-line therapy, breast cancer patients eventually develop resistance. That’s where Bowdish says PIC’s approach can have an impact. As targeted cancer treatments break patients into smaller, more specific groups based on what mutations they carry, PIC is going the opposite way. “What we’re seeing with eIF4E is the opportunity to actually address all of these different tumor drivers. And what this then allows us to do is, rather than fragmenting this large patient population into smaller and smaller subsets, each getting a specific type of drug, we believe we can maintain consolidation of these patients with a single compound, addressing all of them at once,” Bowdish said. Pfizer-partnered eFFECTOR Therapeutics is pursuing a similar approach. Its lead candidate tomivosertib targets MNK1/2, which is part of the same complex as eIF4E, and is in mid-stage studies. And the Pfizer deal is centered around eFFECTOR’s preclinical eIF4E candidates. Eyeing the 'translatome,' Pfizer ties another knot with biotech partner for preclinical, next-gen targeted therapies Bowdish said PIC is currently selecting its lead candidate and hopes to file its IND next year.

SAN DIEGO, July 16, 2021 (GLOBE NEWSWIRE) --eFFECTOR Therapeutics, Inc., , a leader in the development of selective translation regulation inhibitors (“STRIs”) for the treatment of cancer, announced today the publication of data highlighting the role of eukaryotic translation initiation factor 4E (“eIF4E”), in the peer-reviewed journal Cell Reports. eIF4E is a component of the eIF4F complex, which, in conjunction with its activating kinase (“MNK”), triggers an increase in protein synthesis that is critical for cancer growth and immune evasion. The published research, which provides insight into the potential of eIF4E inhibition for the treatment of cancer, was conducted at the University of California, San Francisco in collaboration with eFFECTOR. The eIF4E target is the subject of eFFECTOR’s collaboration with Pfizer. “This publication further validates the novel science on which eFFECTOR’s platform is built,” said Steve Worland, Ph.D., president and CEO of eFFECTOR. “These findings underscore eIF4E’s role as a key hub for regulating cancer drivers such as mitochondrial stress, and the data showed that jointly inhibiting Bcl-xL while blocking eIF4E activation using our MNK 1/2 inhibitor tomivosertib is a promising approach for treating cancer.” “The results in this paper highlight the numerous genetic interactions with eIF4E that may help inform cancer vulnerabilities,” said Davide Ruggero, Ph.D., senior author on the paper; professor at the UCSF Helen Diller Cancer Center; an American Cancer Society Research Professor; and co-founder of eFFECTOR. “Our team is pleased to add to the growing body of scientific research on the interactions between cellular processes that drive cancer and key components of the translation machinery such as eIF4E. We are proud that our contributions have the potential to broaden the treatment landscape for those impacted by cancer.” The Role of eIF4E in Cancer eIF4E is an oncogene and historically intractable target that is activated in a variety of human cancers and is linked to poor prognosis and resistance to certain therapies. eIF4E is an effector protein integrating signals from multiple important oncogenes and tumor suppressor proteins in the PI3K and RAS oncogenic pathways (including PI3K, AKT, mTOR, PTEN and BRAF), and selectively regulates the translation of a set of target mRNA distinct from those regulated by MNK1/2 and eIF4A. This may expand the potential patient population that may benefit from translation regulation therapy. About Tomivosertib (eFT508) Tomivosertib is eFFECTOR’s wholly-owned, highly selective translation regulation inhibitor that targets MNK1 and MNK2 (MNK1/2). The oral, small molecule drug candidate has been shown to enhance killing of tumor cells by T cells, delay T-cell exhaustion/dysfunction and enhance the T-cell central memory pool, in part by down-regulating multiple checkpoint proteins including PD-1, PD-L1, TIM-3 and LAG-3. Tomivosertib is being evaluated in KICKSTART, eFFECTOR’s randomized, double-blind, placebo-controlled Phase 2b study in non-small cell lung cancer (“NSCLC”) in combination with pembrolizumab. The KICKSTART trial builds on results obtained in an earlier study of tomivosertib as an extension of checkpoint inhibitor treatment in patients experiencing insufficient response to an FDA-approved checkpoint inhibitor alone. Please visit for further information on ongoing clinical trials of tomivosertib. About eFFECTOR Therapeutics eFFECTOR is a clinical-stage biopharmaceutical company focused on pioneering the development of a new class of oncology drugs referred to as selective translation regulator inhibitors. eFFECTOR’s STRI product candidates target the eIF4F complex and its activating kinase, mitogen-activated protein kinase 1/2 (MNK 1/2). The eIF4F complex is a central node where two of the most frequently mutated signaling pathways in cancer, the PI3K-AKT and RAS-MEK pathways, converge to activate the translation of select mRNA into proteins that are frequent culprits in key disease-driving processes. Each of eFFECTOR’s product candidates is designed to act on a single protein that drives the expression of multiple functionally related proteins, including oncoproteins and immunosuppressive proteins in T cells, that together control tumor growth, survival and immune evasion. eFFECTOR’s lead product candidate, tomivosertib, is a MNK 1/2 inhibitor, currently being evaluated in KICKSTART, a randomized, double-blind, placebo controlled Phase 2b trial of tomivosertib in combination with pembrolizumab in patients with metastatic NSCLC. Zotatifin, eFFECTOR’s inhibitor of eIF4A, is currently in the dose-escalation portion of a Phase 1/2 trial, with Phase 2a expansion cohorts expected to initiate in the second half of 2021. eFFECTOR has a global collaboration with Pfizer to develop inhibitors of a third target, eIF4E. eFFECTOR plans to evaluate zotatifin as a potential host-directed anti-viral therapy in patients with mild to moderate COVID in collaboration with the University of California, San Francisco, under a $5 million grant sponsored by the Defense Advanced Research Projects Agency. Additional Information and Where to Find It On May 26, 2021, eFFECTOR entered into a definitive Agreement and Plan of Merger (the “Merger Agreement”) with Locust Walk Acquisition Corp. (NASDAQ: LWAC), a special purpose acquisition company, and Locust Walk Merger Sub, Inc., a wholly owned subsidiary of LWAC. In connection with the Merger Agreement, LWAC has filed a registration statement on Form S-4 with the SEC, which includes a document that will serve as a prospectus and proxy statement of LWAC, referred to as a proxy statement/prospectus. A proxy statement/prospectus will be sent to all LWAC stockholders. LWAC also will documents regarding the Merger Agreement and the transactions contemplated thereby (the “Transactions”) with the SEC. Before making any voting decision, investors and security holders of LWAC are urged to read the registration statement, the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC in connection with the Transactions as they become available because they will contain important information about the Transactions, including the terms of the Transactions, the parties involved and the risks associated with the Transactions. Investors and security holders will be able to obtain free copies of the registration statement, the proxy statement/prospectus and all other relevant documents filed or that will be filed with the SEC by LWAC through the website maintained by the SEC at Alternatively, these documents, when available, can be obtained free of charge from LWAC upon written request to Locust Walk Acquisition Corp., c/o eFFECTOR, 11120 Roselle Street, Suite A, San Diego, CA 92121, Attn: Secretary, or by calling (858) 925-8215. Participants in the Solicitation LWAC and eFFECTOR and their respective directors and executive officers may be deemed to be participants in the solicitation of proxies from LWAC’s stockholders in connection with the Transactions. A list of the names of the directors and executive officers of LWAC and information regarding their interests in the Transactions will be contained in the proxy statement/prospectus when available. You may obtain free copies of these documents as described in the preceding paragraph. No Offer or Solicitation This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities or a solicitation of any vote or approval, nor shall there be any sale of any 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 such other jurisdiction. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of the federal securities laws. All statements other than statements of historical facts contained in this press release, including statements regarding the potential that inhibition of eIF4E could broaden the treatment landscape for cancer patients, and the proposed business combination of eFFECTOR and LWAC, are forward-looking statements. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: potential delays in the commencement, enrollment and completion of clinical trials; disruption to eFFECTOR’s operations from the COVID-19 pandemic, including delaying or otherwise disrupting its clinical trials, manufacturing and supply chain; eFFECTOR’s dependence on third parties in connection with product manufacturing and clinical testing; the results of preclinical studies and early clinical trials are not necessarily predictive of future results; the success of eFFECTOR’s clinical trials and preclinical studies for its product candidates; unexpected adverse side effects or inadequate efficacy of eFFECTOR’s product candidates that may limit their development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; risks relating to the proposed business combination, including the risk that the transaction may not be completed in a timely manner or at all; and the risks associated with eFFECTOR’s business and the business combination set forth in the Appendix to the investor presentation filed as Exhibit 99.3 to the Current Report on Form 8-K filed by LWAC on May 27, 2021 . Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond LWAC’s and eFFECTOR’s control, you should not rely on these forward-looking statements as predictions of future events. The foregoing list of factors is not exclusive, and you should carefully consider the foregoing factors and the other risks and uncertainties described in the “Risk Factors” section of LWAC’s Annual Report on Form 10-K for the year ended December 31, 2020 filed with SEC on March 29, 2021, the registration statement on Form S-4 discussed above and other documents filed by LWAC from time to time with the SEC. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements, including the risk that the conditions under the Merger Agreement are not satisfied. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and except as required by law. LWAC and eFFECTOR assume no obligation and do not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Neither LWAC nor eFFECTOR gives any assurance that either LWAC or eFFECTOR or the combined company will achieve its expectations. Contacts: Investors: Stephanie Carrington Westwicke, an ICR Company 646-277-1282 Stephanie.Carrington@westwicke.com Media: Heidi Chokeir, Ph.D. Canale Communications 619-203-5391 heidi.chokeir@canalecomm.com