MNK1 inhibitors(MAP kinase-interacting serine/threonine-protein kinase MNK1 inhibitors), MNK2 inhibitors(MAP kinase-interacting serine/threonine-protein kinase 2 inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersImmune System Diseases+ [1]

Active Indication

Metastatic Colorectal CarcinomaLymphoid LeukemiaPhiladelphia chromosome positive chronic myelogenous leukemia

Inactive Indication

Acute Lymphoblastic LeukemiaAggressive-Phase Chronic Myelocytic LeukemiaBlast Phase Chronic Granulocytic Leukemia

Originator Organization

Experimental Therapeutics Centre

Active Organization

National University of Singapore

Duke University

AUM Biosciences Pte Ltd.Startup

Inactive Organization

Chiltern International, Inc.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Structure

Molecular FormulaC25H20N4O2

InChIKeyFWRFPHJSGLYXTD-UHFFFAOYSA-N

CAS Registry1464151-33-4

Clinical Trials associated with AUM-001

ACTRN12620000572965 / CompletedPhase 1

A Phase 1, Randomized, Double-Blind, Placebo-Controlled StudyTo Evaluate The Safety, Tolerability, And Pharmacokinetics Of Multiple Ascending Doses Of AUM001 In Normal Healthy Volunteers

Start Date27 Nov 2019

Sponsor / Collaborator

AUM Biosciences Pty Ltd.

NCT03414450 / WithdrawnPhase 1IIT

A Phase 1A Dose Escalation and Phase 1B Expansion Study to Evaluate the Safety and Tolerability of ETC-1907206 in Combination With Dasatinib in Advanced Haematologic Malignancies

This study evaluates the use of ETC-1907206 in combination with dasatinib in certain types of blood cancers. The first phase of the study (1A) is designed to find the highest tolerated dose of ETC-1907206, while the second phase (1B) will assess the safety and tolerability of the recommended dose of ETC-1907206. ETC-1907206 has been designed to block the activity of an enzyme of the body known as Mnk kinase, which is thought to be involved in the development of a variety of cancers.

Start Date25 Apr 2018

Sponsor / Collaborator

Experimental Drug Development Centre

[+1]

100 Clinical Results associated with AUM-001

100 Translational Medicine associated with AUM-001

100 Patents (Medical) associated with AUM-001

Literatures (Medical) associated with AUM-001

01 Jul 2021·European journal of medicinal chemistryQ1 · MEDICINE

Progress in developing MNK inhibitors

Q1 · MEDICINE

Review

Author: Jin, Xin ; Yu, Rilei ; Proud, Christopher G ; Wang, Xuemin ; Jiang, Tao

The MNKs (mitogen-activated protein kinase-interacting protein kinases) phosphorylate eIF4E (eukaryotic initiation factor 4 E) at serine 209; eIF4E plays an important role in the translation of cytoplasmic mRNAs, all of which possess a 5' 'cap' structure to which eIF4E binds. Elevated levels of eIF4E, p-eIF4E and/or the MNK protein kinases have been found in many types of cancer, including solid tumors and leukemia. MNKs also play a role in metabolic disease. Regulation of the activities of MNKs (MNK1 and MNK2), control the phosphorylation of eIF4E, which in turn has a close relationship with the processes of tumor development, cell migration and invasion, and energy metabolism. MNK knock-out mice display no adverse effects on normal cells or phenotypes suggesting that MNK may be a potentially safe targets for the treatment of various cancers. Several MNK inhibitors or 'degraders' have been identified. Initially, some of the inhibitors were developed from natural products or based on other protein kinase inhibitors which inhibit multiple kinases. Subsequently, more potent and selective inhibitors for MNK1/2 have been designed and synthesized. Currently, three inhibitors (BAY1143269, eFT508 and ETC-206) are in various stages of clinical trials for the treatment of solid cancers or leukemia, either alone or combined with inhibitors of other protein kinase. In this review, we summarize the diverse MNK inhibitors that have been reported in patents and other literature, including those with activities in vitro and/or in vivo.

01 Dec 2020·Molecular metabolismQ2 · MEDICINE

Disabling MNK protein kinases promotes oxidative metabolism and protects against diet-induced obesity

Q2 · MEDICINE

ArticleOA

Author: Wong, Derick ; Zhao, Jiajun ; Byrne, Christopher D ; Bo, Tao ; Gao, Ling ; Sandeman, Lauren Y ; Page, Amanda J ; Wang, Xuemin ; Proud, Christopher G ; Jensen, Kirk B ; Kang, Wan Xian

OBJECTIVES:

Diet-driven obesity is increasingly widespread. Its consequences pose major challenges to human health and health care systems. There are MAP kinase-interacting kinases (MNKs) in mice, MNK1 and MNK2. Studies have demonstrated that mice lacking either MNK1 or MNK2 were partially protected against high-fat diet (HFD)-induced weight gain and insulin resistance. The aims of this study were to evaluate the phenotype of mice lacking both MNKs when given an HFD, to assess whether pharmacological inhibition of MNK function also protects against diet-induced obesity (DIO) and its consequences and to probe the mechanisms underlying such protection.

METHODS:

Male wild-type (WT) C57Bl6 mice or mice lacking both MNK1 and MNK2 (double knockout, DKO) were fed an HFD or control diet (CD) for up to 16 weeks. In a separate study, WT mice were also given an HFD for 6 weeks, after which half were treated with the recently-developed MNK inhibitor ETC-206 daily for 10 more weeks while continuing an HFD. Metabolites and other parameters were measured, and the expression of selected mRNAs and proteins was assessed.

RESULTS:

MNK-DKO mice were almost completely protected from HFD-induced obesity. Higher energy expenditure (EE) in MNK-DKO mice was observed, which probably reflects the changes in a number of genes or proteins linked to lipolysis, mitochondrial function/biogenesis, oxidative metabolism, and/or ATP consumption. The MNK inhibitor ETC-206 also prevented HFD-induced weight gain, confirming that the activity of the MNKs facilitates weight gain due to excessive caloric consumption.

CONCLUSIONS:

Disabling MNKs in mice, either genetically or pharmacologically, strongly prevents weight gain on a calorie-rich diet. This finding likely results from increased energy utilisation, involving greater ATP consumption, mitochondrial oxidative metabolism, and other processes.

24 May 2018·Journal of medicinal chemistryQ1 · MEDICINE

Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia

Q1 · MEDICINE

Article

Author: Nacro, Kassoum ; Chew, Yun Shan ; Matter, Alex ; Kwek, Perlyn ; Ho, Melvyn Wai Tuck ; Sangthongpitag, Kanda ; Yeap, Yoon Sheng ; Wee, John Liang Kuan ; Pendharkar, Vishal ; Verma, Chandra S. ; Hill, Jeffrey ; Ong, Esther Hq ; Tan, Eldwin Sum Wai ; Joy, Joma Kanikadu ; Yang, Haiyan ; Manoharan, Vithya ; Kannan, Srinivasaraghavan ; Tai, Shi Jing ; Choong, Meng Ling ; Chuah, Charles ; Liu, Boping ; Nguyen, Thuy Thi Hanh ; Lee, May Ann ; Ong, Tiong Sin ; Lim, Sharon ; Jeyaraj, Duraiswamy Athisayamani ; Chennamaneni, Lohitha Rao ; Dinie, Nurul ; Poulsen, Anders ; Vuddagiri, Susmitha ; Ang, Shi Hua ; Low, Choon Bing ; Retna, Priya

Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by bcr-abl1, a constitutively active tyrosine kinase fusion gene responsible for an abnormal proliferation of leukemic stem cells (LSCs). Inhibition of BCR-ABL1 kinase activity offers long-term relief to CML patients. However, for a proportion of them, BCR-ABL1 inhibition will become ineffective at treating the disease, and CML will progress to blast crisis (BC) CML with poor prognosis. BC-CML is often associated with excessive phosphorylated eukaryotic translation initiation factor 4E (eIF4E), which renders LSCs capable of proliferating via self-renewal, oblivious to BCR-ABL1 inhibition. In vivo, eIF4E is exclusively phosphorylated on Ser209 by MNK1/2. Consequently, a selective inhibitor of MNK1/2 should reduce the level of phosphorylated eIF4E and re-sensitize LSCs to BCR-ABL1 inhibition, thus hindering the proliferation of BC LSCs. We report herein the structure-activity relationships and pharmacokinetic properties of a selective MNK1/2 inhibitor clinical candidate, ETC-206, which in combination with dasatinib prevents BC-CML LSC self-renewal in vitro and enhances dasatinib antitumor activity in vivo.

News (Medical) associated with AUM-001

15 Nov 2022

·www.biospace.com

AUM Biosciences Receives Human Research Ethics Committee Approval to Commence Phase II Clinical Trial of AUM001 for Treatment of Metastatic Colorectal Cancer in Australia

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

Phase 2Phase 1ImmunotherapyIND

04 Nov 2022

·www.biospace.com

AUM Biosciences to Participate in BioCentury-BayHelix East-West BioPharma Summit

SINGAPORE and BETHESDA, Md., Nov. 04, 2022 (GLOBE NEWSWIRE) -- AUM Biosciences Pte. Ltd. (“AUM”), a clinical-stage biotechnology company, advancing a clinical-stage pipeline of precision oncology therapeutics designed to deploy multi-faceted inhibition strategies to reverse cancer resistance, announced today that their management team will participate in the BioCentury-BayHelix East-West BioPharma Summit in Redwood City, California and virtually. Vishal Doshi, founder and Chief Executive Officer of AUM, is scheduled to participate on Tuesday, November 15th at 10:30 am PT on a panel entitled, “CEO Roundtable: What Will it Take to be Successful in the Next Era of Biotech?” In addition, the management team will host investor meetings at the conference. As previously announced on October 20, 2022, AUM has entered into a definitive business combination agreement (the “Agreement”) with Mountain Crest Acquisition Corp. V (“Mountain Crest”) (Nasdaq: MCAG), a publicly-traded special purpose acquisition company formed in Delaware, whose management team has an impressive pedigree of successful SPAC transactions. Upon the closing of the business combination, anticipated to occur in the first quarter of 2023, AUM plans to operate under a holding entity, AUM Biosciences Limited, a Cayman Islands exempted company, 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 clinical-stage 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 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. Contact: 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

First in ClassSmall molecular drugIPOAcquisition

21 Oct 2022

·www.fiercebiotech.com

SPAC in fashion: Cancer-focused Aum is latest biotech to use blank check route

A new deal should give Aum Biosciences access to around $69 million from Mountain Crest’s trust account. Whisper it, but biotech SPACs appear to be back in fashion. The latest is cancer-focused Aum Biosciences, which is merging with blank check company Mountain Crest Acquisition to put its MNK and TRK inhibitors into phase 2 testing. The transaction—which is expected to close in the first quarter of 2023—will see Aum’s private company stock converted into 40 million shares of a holding company priced at $10 a pop, representing an equity value for the newly merged company of $400 million. The price tag reflects a perceived $10 billion market opportunity in metastatic colorectal cancer as well as TRK fusion and mutation cancers, according to the companies. The Singapore-based biotech’s lead asset is AUM001, a selective and synergistic MNK inhibitor that is expected to enter phase 2 trials in metastatic colorectal cancer by the end of the year, both as monotherapy and in combination with Merck & Co.’s Keytruda. The therapy also has another Big Pharma team-up in the works, thanks to a partnership with Roche to assess a combination with Tecentriq on solid tumor indications. Further down AUM’s pipeline is AUM601, a phase 1 therapy for TRK fusions and mutations within the kinase domain. TRK is a target of Bayer’s Vitrakvi, Roche’s Rozlytrek and a clutch of investigational drug candidates designed to address the resistance tumors can acquire against the molecules. Yet to make it to the clinic is another macrocyclic oral kinase inhibitor called AUM302, as well as AUM003, a potential blood brain barrier-penetrating selective MNK inhibitor. “AUM is a unique and compelling investment opportunity, with its clinical-stage diversified pipeline of precision therapeutic candidates and global strategic partnerships with industry heavyweights, pointing to significant future growth potential and allowing the company to have a greater U.S. footprint,” Mountain Crest CEO Suying Liu, Ph.D., said in the release Thursday. Aum has been living off a $27 million series A funding round from October 2021, but the special purpose acquisition deal should give Aum access to around $69 million from Mountain Crest’s trust account. Plus, selling the Chinese rights for AUM001, AUM302 and AUM003 to Newsoara also means the company could be entitled to a windfall of up to $135 million in biobucks if the three candidates pan out. Aum CEO Vishal Doshi will continue to head up the publicly listed company, which will trade on the Nasdaq under the ticker "AUMB." Once an industry staple, so-called blank check deals in biotech were all but left for dead at the start of 2022, with zero SPAC mergers occurring in the first quarter. But the last few months have seen a steady, if shallow, stream of SPAC deals, including Oculis and Estrella Biopharma also announcing their intentions in October.

AcquisitionCollaborate

100 Deals associated with AUM-001

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Colorectal Carcinoma	Phase 2	AU	AUM Biosciences Pte Ltd.Startup	15 Nov 2022
Hematologic Neoplasms	Phase 1	SG	AUM Biosciences Pte Ltd.Startup	06 Jan 2020
Acute Lymphoblastic Leukemia	Phase 1	US	Chiltern International, Inc.	25 Apr 2018
Acute Lymphoblastic Leukemia	Phase 1	SG	Chiltern International, Inc.	25 Apr 2018
Aggressive-Phase Chronic Myelocytic Leukemia	Phase 1	US	Chiltern International, Inc.	25 Apr 2018
Aggressive-Phase Chronic Myelocytic Leukemia	Phase 1	SG	Chiltern International, Inc.	25 Apr 2018
Blast Phase Chronic Granulocytic Leukemia	Phase 1	US	Chiltern International, Inc.	25 Apr 2018
Blast Phase Chronic Granulocytic Leukemia	Phase 1	SG	Chiltern International, Inc.	25 Apr 2018
Lymphoid Leukemia	Phase 1	-	National University of Singapore	-
Lymphoid Leukemia	Phase 1	-	Duke University	-

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