July 2022 - Acer Therapeutics

Acer Therapeutics and Relief Therapeutics Announce ACER-001 IND Submission for the Treatment of Maple Syrup Urine Disease

Posted on July 28, 2022July 28, 2022 by AcerUser

NEWTON, MA and GENEVA, SWITZERLAND – July 28, 2022 – Acer Therapeutics Inc. (Nasdaq: ACER) (Acer) and its collaboration partner, RELIEF THERAPEUTICS Holding SA (SIX: RLF, OTCQB: RLFTF, RLFTY) (Relief), today announced the submission of an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) to evaluate the efficacy and safety of ACER-001 (sodium phenylbutyrate) for the potential treatment of patients with Maple Syrup Urine Disease (MSUD).

MSUD is a rare, life-threatening metabolic disorder caused by a deficiency in an enzyme complex that metabolizes branched chain ketoacids, the breakdown products of the three branched-chain amino acids (BCAAs), leucine, valine, and isoleucine. Left untreated, MSUD leads to elevated plasma concentrations of these amino acids, which can lead to chronic and acute neurological damage, ranging from developmental delays in children, seizures, cognitive challenges and in some cases death. Currently, the only treatment option for patients with MSUD is a life-long, protein-restricted diet.

“We are very pleased to expand ACER-001’s clinical development into a second rare disease, and one for which there are currently no approved pharmacologic therapies,” said Adrian Quartel, MD, FFPM, Chief Medical Officer of Acer. “Even with strict dietary management, people with MSUD still remain at serious risk for a wide range of life-threatening complications. We look forward to the initiation of this investigational trial and learning more about ACER-001’s potential to reduce branched-chain amino acids, and specifically leucine levels, in MSUD patients.”

The proposed initial Phase 2a, open-label dose-ranging trial is designed to evaluate the effect of different doses of ACER-001 (sodium phenylbutyrate) on blood leucine and other branched-chain amino acid (BCAA) levels in MSUD patients.

Rationale for ACER-001 Treatment in MSUD
Multiple investigational trials evaluating sodium phenylbutyrate in urea cycle disorder (UCD) patients suggest treatment with sodium phenylbutyrate is associated with selective reduction in BCAA despite adequate dietary protein intake.^1,2,3,4 Analysis of data from a longitudinal multicenter study of 553 UCD patients treated with sodium phenylbutyrate demonstrated that sodium phenylbutyrate decreased plasma BCAA in patients with UCDs and could serve as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism.²

Based on this clinical observation, investigators at Baylor College of Medicine explored the potential of sodium phenylbutyrate treatment to lower BCAA and corresponding branched-chain α-ketoacid (BCKA) levels in both healthy subjects and patients with MSUD. The investigators found that sodium phenylbutyrate, when dosed over three days, showed a statistically significant reduction of leucine in all three healthy subjects and in three out of the five MSUD patients who participated in the trial.⁵

In November 2020, study results evaluating the effect of sodium phenylbutyrate in the management of acute metabolic decompensation in pediatric MSUD patients (n=10) were published by investigators from Istanbul University-Cerrahpasa Medical Faculty in the peer-reviewed Journal of Pediatric Endocrinology and Metabolism showing a significant reduction in leucine levels in MSUD patients experiencing an acute attack.⁶ The results suggested that sodium phenylbutyrate could be safely administered in combination with emergency protocol using other active pharmaceuticals and may provide additional clinical benefit beyond emergency protocol alone.

About MSUD
MSUD is a rare inherited disorder caused by a deficiency of branched-chain alpha-keto acid dehydrogenase complex, resulting in elevated blood levels of the branched-chain amino acids (BCAA) leucine, valine, and isoleucine, as well as the associated branched-chain ketoacids (BCKA) in a patient’s blood. Left untreated, this can result in neurological damage, mental disability, coma, or death. The most severe presentation of MSUD, known as “classic” MSUD, accounts for 80% of cases and can result in neonatal onset with encephalopathy and coma. Although metabolic management of the disease is possible via a highly restrictive diet, the outcome is unpredictable, and a significant portion of affected individuals are mentally impaired or experience neurological complications.

MSUD is typically diagnosed at birth via newborn screening and incidence is estimated at 1 in 185,000 people worldwide and 1 in 220,000 people in the United States.⁷ The disorder occurs more frequently in the Old Order Mennonite population, with an estimated incidence of about 1 in 380 newborns, and the Ashkenazi Jewish population, with an estimated incidence of 1 in 26,000.⁸

About ACER-001
ACER-001 (sodium phenylbutyrate) is being developed for the treatment of various inborn errors of metabolism, including UCDs and Maple Syrup Urine Disease (MSUD). ACER-001 (sodium phenylbutyrate) is an immediate-release, polymer coated, multi-particulate formulation of sodium phenylbutyrate for oral administration via suspension, that is designed to improve palatability. ACER‑001 (sodium phenylbutyrate) has been granted orphan drug designation by the FDA for MSUD. In July 2022, Acer resubmitted its New Drug Application (NDA) to the FDA for ACER-001 (sodium phenylbutyrate) for oral suspension for the treatment of patients with UCDs in response to the FDA’s Complete Response Letter. This investigational product candidate has not been approved by FDA, the European Medicines Agency (EMA), or any other regulatory authority. There can be no assurance that the resubmitted ACER-001 NDA for UCDs will be approved by the FDA, or that ACER-001 (sodium phenylbutyrate) will otherwise be approved for any indication.

About Acer Therapeutics Inc.
Acer is a pharmaceutical company focused on the acquisition, development and commercialization of therapies for serious rare and life-threatening diseases with significant unmet medical needs. Acer’s pipeline includes four investigational programs: ACER-001 (sodium phenylbutyrate) for treatment of various inborn errors of metabolism, including urea cycle disorders (UCDs) and Maple Syrup Urine Disease (MSUD); ACER-801 (osanetant) for treatment of induced Vasomotor Symptoms (iVMS); EDSIVO™ (celiprolol) for treatment of vascular Ehlers-Danlos syndrome (vEDS) in patients with a confirmed type III collagen (COL3A1) mutation; and ACER-2820 (emetine), a host-directed therapy against a variety of viruses, including cytomegalovirus, Zika, dengue, Ebola and COVID-19. For more information, visit www.acertx.com.

About RELIEF THERAPEUTICS Holding SA
Relief focuses primarily on clinical-stage programs based on molecules with a history of clinical testing and use in human patients or a strong scientific rationale. Relief has a Collaboration and License Agreement with Acer Therapeutics for the worldwide development and commercialization of ACER-001 (sodium phenylbutyrate) for the treatment of various inborn errors of metabolism, including UCDs and Maple Syrup Urine Disease (MSUD). Relief also continues to study aviptadil for several possible lung related conditions. Finally, Relief’s 2021 acquisitions of APR Applied Pharma Research SA and AdVita Lifescience GmbH brought to Relief a diverse pipeline of marketed and development-stage programs.

RELIEF THERAPEUTICS Holding SA is listed on the SIX Swiss Exchange under the symbol RLF and quoted in the U.S. on OTCQB under the symbols RLFTF and RLFTY. For more information, visit www.relieftherapeutics.com Follow Relief on LinkedIn.

References

Muelly 2011 Neuropsychiatric and Neurochemical Sequelae of MSUD.
L.C. Burrage, et al., Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders, Mol. Genet. Metab. (2014)
Scaglia F. New insights in nutritional management and amino acid supplementation in urea cycle disorders. Mol Genet Metab. 2010;100 Suppl 1(Suppl 1):S72-6.
Häberle, J., Boddaert, N., Burlina, A. et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis 7, 32 (2012)
Brunetti-Pierri et al. Phenylbutyrate therapy for maple syrup urine disease. Hum Mol Genet. 2011 February 15; 20(4): 631–640.
Zubarioglu T, et al. Impact of sodium phenylbutyrate treatment in acute management of maple syrup urine disease attacks: a single-center experience. J Pediatr Endocrinol Metab. 2020 Nov 11;34(1):121-126.
Chapman, K, et al. (2018). Incidence of maple syrup urine disease, propionic acidemia, and methylmalonic aciduria from newborn screening data. Molecular Genetics and Metabolism Reports. 15. 106-109.
Strauss KA, et al. Maple Syrup Urine Disease. In: Pagon RA, Adam MP, Ardinger HH, al. e, eds. GeneReviews® [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK1319/: University of Washington, Seattle; 2006. Accessed March 22, 2017

Relief Forward-Looking Statements
This communication expressly or implicitly contains certain forward-looking statements concerning RELIEF THERAPEUTICS Holding SA and its businesses. Such statements involve certain known and unknown risks, uncertainties and other factors, including (i) whether the FDA will approve Acer’s NDA for ACER-001 for the treatment of UCDs, (ii) whether RELIEF THERAPEUTICS Holding SA will submit an application for approval of ACER-001 in Europe for the treatment of UCDs and the timing of filing such application, (iii) whether any application submitted to European authorities seeking marketing authorization for ACER-001 for the treatment of patients in Europe with UCDs will be approved, (iv) whether the FDA will approve Acer’s IND to evaluate ACER-001 for the treatment of MSUDs, (v) the timing of Acer’s Phase 2b trial evaluating ACER-001 for the treatment of MSUDs, (vi) whether ACER-001’s currently proposed trial and any future required trials of ACER-001 for MSUDs will be undertaken and successful, (vii) whether ACER-001 will ever be approved for the treatment of MSUDs in the United States, (viii) whether Relief will ever file the necessary applications in Europe to seek the right to commercialize ACER-001 in Europe for the treatment of MSUDs and whether any such applications filed will be granted, and (ix) those other risks, uncertainties and factors described in RELIEF THERAPEUTICS Holding SA’s press releases and filings with the SIX Swiss Exchange and the U.S. Securities and Exchange Commission, all of which could cause the actual results, financial condition, performance or achievements of RELIEF THERAPEUTICS Holding SA to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. RELIEF THERAPEUTICS Holding SA is providing this communication as of this date and does not undertake to update any forward-looking statements contained herein as a result of new information, future events or otherwise.

CORPORATE CONTACTS

Acer Therapeutics:
Jim DeNike
Acer Therapeutics Inc.
jdenike@ktharaldsenacertx-com
+1-844-902-6100

RELIEF Therapeutics Holding SA:
Jack Weinstein
Chief Financial Officer and Treasurer
contact@relieftherapeutics.com

INVESTOR RELATIONS CONTACTS

Acer Therapeutics:
Nick Colangelo
Gilmartin Group
nick@gilmartinIR.com
+1-332-895-3226

Relief Therapeutics Holding SA:
Michael Miller
Rx Communications Group
mmiller@rxir.com
+1-917-633-6086

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Acer Therapeutics and Relief Therapeutics Announce FDA Acceptance for Review of NDA Resubmission for ACER-001 for Treatment of UCDs

Posted on July 28, 2022July 28, 2022 by AcerUser

NEWTON, MA and GENEVA, SWITZERLAND – July 28, 2022 – Acer Therapeutics Inc. (Nasdaq: ACER) (Acer) and its collaboration partner, RELIEF THERAPEUTICS Holding SA (SIX: RLF, OTCQB: RLFTF, RLFTY) (Relief), today announced the U.S. Food and Drug Administration (FDA) has accepted for review Acer’s resubmitted New Drug Application (NDA) for ACER-001 (sodium phenylbutyrate) for oral suspension for the treatment of patients with urea cycle disorders (UCDs). The FDA designated the NDA as a Class 2 resubmission and set a Prescription Drug User Fee Act (PDUFA) target action date of January 15, 2023.

“We are very pleased to receive confirmation that the FDA is commencing its review of our NDA resubmission,” said Chris Schelling, Founder & Chief Executive Officer of Acer. “We have notified the FDA that our third-party contract packaging manufacturer is ready for inspection and are hopeful that the Agency’s review can be completed in a timely manner. While NDA approval is not assured, if approval is received, we are prepared to execute on our comprehensive launch plan and provide a new treatment option to underserved UCDs patients. These efforts reinforce our ongoing commitment to developing new and differentiated treatment options for those affected by rare diseases.”

In June 2022, as previously announced, the FDA issued Acer a Complete Response Letter (CRL) stating that satisfactory inspection of Acer’s third-party contract packaging manufacturer is required before the ACER-001 NDA may be approved. Acer notified the FDA in the NDA resubmission that the third-party contract packaging manufacturer is ready for inspection. The FDA did not cite any other approvability issues in the CRL pertaining to the NDA, nor request any additional clinical or pharmacokinetic studies be conducted prior to FDA action. Additional existing nonclinical information as requested by the FDA in the CRL but identified as “not an approvability issue”, as well as labeling and other required updates to the original NDA, were provided in the resubmission of the NDA.

There can be no assurance that ACER-001 will be approved for any indication.

CORPORATE CONTACTS

Acer Therapeutics:
Jim DeNike
Acer Therapeutics Inc.
jdenike@ktharaldsenacertx-com
+1-844-902-6100

RELIEF Therapeutics Holding SA:
Jack Weinstein
Chief Financial Officer and Treasurer
contact@relieftherapeutics.com

INVESTOR RELATIONS CONTACTS

Acer Therapeutics:
Nick Colangelo
Gilmartin Group
nick@gilmartinIR.com
+1-332-895-3226

Relief Therapeutics Holding SA:
Michael Miller
Rx Communications Group
mmiller@rxir.com
+1-917-633-6086

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Acer Therapeutics Announces Resubmission of New Drug Application for ACER-001 for Treatment of UCDs

Posted on July 18, 2022July 18, 2022 by AcerUser

NEWTON, MA – July 18, 2022 – Acer Therapeutics Inc. (Nasdaq: ACER), a pharmaceutical company focused on the acquisition, development and commercialization of therapies for serious rare and life-threatening diseases with significant unmet medical needs, today announced the resubmission of Acer’s New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ACER-001 (sodium phenylbutyrate) for oral suspension for the treatment of patients with urea cycle disorders (UCDs). Acer believes the resubmission addresses in full the items raised by the FDA in the Complete Response Letter (CRL).

In June 2022, as previously announced, the FDA issued Acer a CRL stating that satisfactory inspection of its third-party contract packaging manufacturer is required before the ACER-001 NDA may be approved. Acer notified the FDA in the resubmission that the third-party contract packaging manufacturer is ready for inspection. FDA did not cite any other approvability issues in the CRL pertaining to the NDA, nor request any additional clinical or pharmacokinetic studies be conducted prior to FDA action. Additional existing nonclinical information as requested by the FDA in the CRL but identified as “not an approvability issue”, as well as labeling and other routine updates to the original NDA, were provided in the resubmission of the NDA.

“Our team did an outstanding job resubmitting the NDA one month after we received the CRL,” said Chris Schelling, Founder & Chief Executive Officer of Acer. “Our third-party contract manufacturing partner has been incredibly responsive and has confirmed that it is ready for inspection. Our manufacturing partner is regarded as a global leader in clinical supply chain and commercial packaging services with more than 70 years of experience. Along with the other requested updates we provided to the FDA in our resubmitted NDA, assuming it is accepted for review, we now look forward to assisting the FDA in the completion of its review of our NDA as soon as possible.”

Acer expects to be notified by the Agency of its decision to accept or reject the resubmission for review within 14 calendar days of receipt of the NDA resubmission.¹ If the resubmission is deemed complete by the FDA, a resubmission classification (Class 1 or 2) will be assigned and a new Prescription Drug User Fee Act (PDUFA) target action date will be established of either two or six months from the resubmission date depending on the classification and an inspection of the facility will be requested. However, there can be no assurance the resubmission will be accepted for review, classified for action, or the target action deadline will be established or met.

About ACER-001
ACER-001 (sodium phenylbutyrate) is being developed for the treatment of various inborn errors of metabolism, including UCDs and Maple Syrup Urine Disease (MSUD). ACER-001 is a nitrogen-binding agent in development for use as adjunctive therapy in the chronic management of patients with UCDs involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). ACER-001 is a polymer coated formulation that, when taken within 5 minutes, helps prevent the coating from dissolving. ACER-001 has been granted orphan drug designation by the FDA for MSUD. ACER-001 is an investigational product candidate which has not been approved by FDA, the European Medicines Agency (EMA), or any other regulatory authority. There can be no assurance that the FDA inspection of the third-party contract packaging manufacturer facility will be satisfactory, that such inspection is the only impediment to FDA approval of a resubmitted NDA, that a resubmitted NDA will otherwise be approved by the FDA, or that ACER-001 will be approved for any indication.

References

FDA SOPP 8405.1: Procedures for Resubmissions to an Application or Supplement Version: 7 Effective Date: November 1, 2021 https://www.fda.gov/media/84417/download

CORPORATE CONTACTS
Jim DeNike
Acer Therapeutics Inc.
jdenike@acertx.com
+1-844-902-6100

INVESTOR RELATIONS CONTACTS
Nick Colangelo
Gilmartin Group
nick@gilmartinIR.com
+1-339-225-1047

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Acer Therapeutics and Relief Therapeutics Announce That the China National Intellectual Property Administration (CNIPA) Issued Utility Model Patent 11,202,767 Covering ACER-001 Dosage Form

Posted on July 8, 2022July 8, 2022 by AcerUser

NEWTON, MA and GENEVA, SWITZERLAND – July 8, 2022 – Acer Therapeutics Inc. (Nasdaq: ACER) (Acer) and its collaboration partner, RELIEF THERAPEUTICS Holding SA (SIX: RLF, OTCQB: RLFTF, RLFTY) (Relief), today announced that the China National Intellectual Property Administration (CNIPA) issued Electronic Patent Certificate ZL202122004991.9 on May 24, 2022, for Utility Model directed to ACER-001 (sodium phenylbutyrate). Specifically, the newly issued patent covers dosage form claims related to ACER-001’s polymer coated formulation for oral administration as a potential treatment for urea cycle disorders (UCDs) and Maple Syrup Urine Disease (MSUD). The newly issued patent has an expiration date of August 24, 2031.

“The receipt of this patent from the CNIPA for ACER-001, is an important milestone for Acer and Relief, adding key protection to the growing intellectual portfolio of this coated formulation of sodium phenylbutyrate, which could be an important treatment for patients with UCDs and we hope to extend its use as a potential treatment for MSUD and other indications,” stated Raghuram (Ram) Selvaraju, Chairman of Relief. “The issuance of this patent also marks an important step in our pursuit of possible ACER-001 commercialization in China.”

About ACER-001
ACER-001 (sodium phenylbutyrate) is being developed for the treatment of various inborn errors of metabolism, including UCDs and Maple Syrup Urine Disease (MSUD). ACER-001 is a nitrogen-binding agent in development for use as adjunctive therapy in the chronic management of patients with UCDs involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). ACER-001 is a polymer coated formulation that, when taken within 5 minutes, helps prevent the coating from dissolving. ACER-001 has been granted orphan drug designation by the FDA for MSUD. ACER-001 is an investigational product candidate which has not been approved by FDA, the European Medicines Agency (EMA), or any other regulatory authority. There can be no assurance that Acer will be able to meet its intended resubmission timeline for the NDA, that FDA inspection of the third-party contract packaging manufacturer facility will be satisfactory, that such inspection is the only impediment to FDA approval of a resubmitted NDA, that a resubmitted NDA will otherwise be approved by the FDA, or that ACER-001 will be approved for any indication.

About RELIEF
Relief focuses primarily on clinical-stage programs based on molecules with a history of clinical testing and use in human patients or a strong scientific rationale. Relief has a Collaboration and License Agreement with Acer Therapeutics for the worldwide development and commercialization of ACER-001 (sodium phenylbutyrate) for the treatment of various inborn errors of metabolism, including UCDs and Maple Syrup Urine Disease (MSUD). Relief also continues to study aviptadil for several possible lung related conditions. Finally, Relief’s 2021 acquisitions of APR Applied Pharma Research SA and AdVita Lifescience GmbH brought to Relief a diverse pipeline of marketed and development-stage programs.

Acer Forward-Looking Statements
This press release contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release regarding strategy, future operations, timelines for clinical study enrollment or regulatory actions, or otherwise, future financial position, future revenues, projected expenses, regulatory submissions, actions or approvals, cash position, liquidity, prospects, plans and objectives of management are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to the potential for our investigational product candidates to safely and effectively treat diseases and to be approved for marketing; our ability to submit regulatory filings (including for ACER-001 for oral suspension for the treatment of patients with UCDs) within intended timeframes, to address satisfactorily the requirements for regulatory approval (including through FDA inspection of our third-party contract packaging manufacturer for ACER-001 for oral suspension for the treatment of patients with UCDs), or to otherwise address satisfactorily the requirements for and to obtain regulatory approval (including approval by the FDA of a resubmitted NDA for ACER-001 for oral suspension for the treatment of patients with UCDs); our ability to close upon and obtain the proceeds of any financing arrangements as well as to satisfy the ongoing conditions and requirements for maintaining the financing facilities and avoiding default or an accelerated payment requirement; the commercial or market opportunity of any of our product candidates in any target indication and any territory; our ability to secure the additional capital necessary to fund our various product candidate development programs; the adequacy of our capital to support our future operations and our ability to successfully fund, initiate and complete clinical trials and regulatory submissions for ACER-001, ACER-801, EDSIVO™ or our other product candidates; the ability to protect our intellectual property rights; our strategy and business focus; and the development, expected timeline and commercial potential of any of our product candidates. Our pipeline products are under investigation and their safety and efficacy have not been established and there is no guarantee that any of our investigational products in development will receive health authority approval or become commercially available for the uses being investigated. We may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements and you should not place undue reliance on these forward-looking statements. Such statements are based on management’s current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward-looking statements as a result of many factors, including, without limitation, risks and uncertainties associated with the ability to project future cash utilization and reserves needed for contingent future liabilities and business operations, the availability of sufficient resources to fund our various product candidate development programs and to meet our business objectives and operational requirements, the fact that the results of earlier studies and trials may not be predictive of future clinical trial results, the protection and market exclusivity provided by our intellectual property, risks related to the drug development and the regulatory approval process, including the timing and requirements of regulatory actions, and the impact of competitive products and technological changes. We disclaim any intent or obligation to update these forward-looking statements to reflect events or circumstances that exist after the date on which they were made. You should review additional disclosures we make in our filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. You may access these documents for no charge at http://www.sec.gov.

CORPORATE CONTACTS

Acer Therapeutics:
Jim DeNike
Acer Therapeutics Inc.
jdenike@acertx.com
+1-844-902-6100

RELIEF Therapeutics Holding SA:
Jack Weinstein
Chief Financial Officer and Treasurer
contact@relieftherapeutics.com

INVESTOR RELATIONS CONTACTS

Acer Therapeutics:
Nick Colangelo
Gilmartin Group
nick@gilmartinIR.com
+1-339-225-1047

Relief Therapeutics Holding SA:
Michael Miller
Rx Communications Group
mmiller@rxir.com
+1-917-633-6086

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