Auris Medical to Develop KRAS-Targeting RNA Treatment for Colorectal Cancer as First Therapeutic Indication for OligoPhore™ Technology

Rhea-AI Summary

Auris Medical Holding Ltd. (NASDAQ: EARS) announced the selection of KRAS-driven colorectal cancer as the first indication for its OligoPhore™ platform. The development program, designated AM-401, aims for IND submission by late 2022. With colorectal cancer being the second leading cause of cancer death in the U.S., the company's research highlights a significant unmet medical need. Preclinical studies demonstrated effective KRAS silencing and tumor growth inhibition using OligoPhore™ technology, showcasing its potential in targeted cancer therapeutics.

Positive

• KRAS-driven colorectal cancer chosen as the initial indication for OligoPhore™ platform.
• Targeting IND submission by late 2022 under project code AM-401.
• Preclinical studies show successful KRAS silencing and reduced tumor growth in colorectal cancer models.

Negative

• None.

• Treatment of KRAS-driven colorectal cancer selected as first therapeutic indication for OligoPhore™ platform
• Company to launch development program under project code AM-401 with aim of IND submission in late 2022

Hamilton, Bermuda, July 6, 2021 – Auris Medical Holding Ltd. (NASDAQ: EARS), a company dedicated to addressing unmet medical needs through RNA therapeutics, allergy and viral infection protection, and inner ear therapeutics, today announced the selection of mutant KRAS-driven colorectal cancer as the first therapeutic indication for its OligoPhore™ oligonucleotide delivery platform. The Company intends to develop the treatment under project code AM-401 with submission of an IND targeted for the end of 2022.

Addressing high unmet medical need

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer death in the US.¹ In 2021, there will be an estimated 149,500 new cases of CRC in the US, and 52,980 deaths from CRC.² Approximately 40 to 50% of patients with CRC harbor mutations of the KRAS gene,³ which are known to contribute to the development, invasion and metastasis of CRC. KRAS encodes the Ras protein which controls - like an “on / off switch” – cell growth, cell maturation, and cell death. Through the mutations, the Ras proteins can be rendered persistently active, causing cancer cells to grow and spread in the body.

Beside CRC, KRAS mutations are frequently observed in pancreatic cancer and lung cancer. Approximately 19% of patients with cancer harbor Ras mutations, equivalent to approximately 3.4 million new cases per year worldwide.⁴ Mutations in KRAS alone account for approximately one million deaths per year worldwide.⁵ Although the role of KRAS mutations in cancer has been known for decades, they have remained a challenging target for therapeutic interventions. Only recently two small molecule inhibitors of single KRAS mutations were approved in a breakthrough by the Food and Drug Administration (FDA) for use in the treatment of non-small cell lung cancer (NSCLC).

Compelling results in KRAS-driven models of colorectal and pancreatic cancer

The selection of CRC as the first therapeutic indication for the OligoPhore™ technology was made based on the high unmet medical need, compelling outcomes from studies with OligoPhore™ enabled KRAS silencing, and a well-defined regulatory and development pathway. In vitro and in vivo experiments conducted jointly by research teams from Washington University, St. Louis MO and the University of South Florida, Tampa FL, demonstrated efficient uptake of OligoPhore™ nanoparticles with KRAS-targeted siRNA in colorectal and pancreatic cancer cells, strong inhibition of KRAS expression, reduced viability of tumor cells and significant reduction in tumor growth and volume.⁶ Importantly, a murine model demonstrated the capacity of the OligoPhore™ platform to drive targeted delivery of the nanoparticles specifically to tumor cells.

“In our preclinical studies with OligoPhore enabled siRNA delivery, we have demonstrated potent knock down of KRAS in a highly targeted and effective fashion, which inhibited a key driver of cancer cell proliferation and metastases”, commented Samuel Wickline, MD, Auris Medical’s Chief Scientific Officer. “Based on these compelling data and the results from our extensive review of strategic development options, we look forward to advancing OligoPhore first in colorectal cancer before applying the technology also to other therapeutic indications. Thanks to its flexibility and specificity, OligoPhore can be used to simultaneously deliver different siRNA payloads for broad target inhibition, which opens exciting novel therapeutic options.”

About OligoPhore™

OligoPhore™ is a versatile platform for safe and effective delivery of oligonucleotides such as siRNA (small interfering ribonucleic acid) into target cells, using systemic or local administration. It is based on a proprietary 21 amino acid peptide that can engage any type of RNA, including mRNA, in rapid self-assembly into a polyplex. The polyplex has a size, charge, and other physical features that allow it to escape hepatic clearance and thus to reach other target tissues than the liver. OligoPhore™ protects the RNA payload from degradation in the circulation and allows for rapid cellular uptake, while enabling pH-dependent nucleotide full endosomal escape and cytoplasmic delivery. Effective delivery and positive treatment outcomes have been demonstrated in more than 10 diverse murine models of disease for cancer, cardiovascular, and rheumatological targets in the NF-κB family, various members of the ETS transcription factor family, and targets in the JNK and TAM pathways.

About Auris Medical

Auris Medical is dedicated to developing therapeutics that address important unmet medical needs. The Company is currently active in three areas: the development of RNA therapeutics for extrahepatic therapeutic targets (OligoPhore™ / SemaPhore™ platforms; preclinical), nasal sprays for protection against airborne viruses and allergens (Bentrio™; pre-commercial) or the treatment of vertigo (AM-125; Phase 2), and the development of therapeutics for intratympanic treatment of tinnitus or hearing loss (Keyzilen® and Sonsuvi®, Phase 3). The Company was founded in 2003 and is headquartered in Hamilton, Bermuda with its main operations in Basel, Switzerland. The shares of Auris Medical Holding Ltd. trade on the NASDAQ Capital Market under the symbol “EARS.” The Company will change its name to “Altamira Therapeutics Ltd.” and its ticker symbol to “CYTO”, subject to approval by a Special General Meeting of shareholders to be held on July 21, 2021.

Forward-looking Statements

This press release may contain statements that constitute “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are statements other than historical facts and may include statements that address future operating, financial or business performance or Auris Medical’s strategies or expectations. In some cases, you can identify these statements by forward-looking words such as “may”, “might”, “will”, “should”, “expects”, “plans”, “anticipates”, “believes”, “estimates”, “predicts”, “projects”, “potential”, “outlook” or “continue”, or the negative of these terms or other comparable terminology. Forward-looking statements are based on management’s current expectations and beliefs and involve significant risks and uncertainties that could cause actual results, developments and business decisions to differ materially from those contemplated by these statements. These risks and uncertainties include, but are not limited to, the approval and timing of commercialization of AM-301, Auris Medical’s need for and ability to raise substantial additional funding to continue the development of its product candidates, the timing and conduct of clinical trials of Auris Medical’s product candidates, the clinical utility of Auris Medical’s product candidates, the timing or likelihood of regulatory filings and approvals, Auris Medical’s intellectual property position and Auris Medical’s financial position, including the impact of any future acquisitions, dispositions, partnerships, license transactions or changes to Auris Medical’s capital structure, including future securities offerings. These risks and uncertainties also include, but are not limited to, those described under the caption “Risk Factors” in Auris Medical’s Annual Report on Form 20-F for the year ended December 31, 2020, and in Auris Medical's other filings with the SEC, which are available free of charge on the Securities Exchange Commission's website at: www.sec.gov. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those indicated. All forward-looking statements and all subsequent written and oral forward-looking statements attributable to Auris Medical or to persons acting on behalf of Auris Medical are expressly qualified in their entirety by reference to these risks and uncertainties. You should not place undue reliance on forward-looking statements. Forward-looking statements speak only as of the date they are made, and Auris Medical does not undertake any obligation to update them in light of new information, future developments or otherwise, except as may be required under applicable law.

Investor contact:

investors@aurismedical.com

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1 Benson AB et al. (2021), NCCN clinical practice guidelines in oncology, colon cancer, version 2.2021, JNCCN 19(3):329-59.
2 National Cancer Institute, https://seer.cancer.gov/statfacts/html/colorect.html
3 Armstrong SA et al. (2020), Molecular profiling in metastatic colorectal cancer, Oncology (Williston Park) 34(9):352-5.
4 Prior IA et al. (2020), The frequency of Ras mutations in cancer, Cancer Res 80(14):2969-74.
5 Simanshu DK et al. (2017), RAS proteins and their regulators in human disease, Cell 170(1):17-33.

6 Strand MS et al. (2019), Precision Delivery of RAS-inhibiting siRNA to KRAS driven cancer via peptide-based nanoparticles, OncoTarget 10(46):4761-75.

FAQ

What is the first therapeutic indication selected for OligoPhore™?

The first therapeutic indication selected for OligoPhore™ is KRAS-driven colorectal cancer.

When does Auris Medical plan to submit the IND for AM-401?

Auris Medical plans to submit the IND for AM-401 by late 2022.

Why is KRAS-driven colorectal cancer significant?

KRAS-driven colorectal cancer is significant due to its high prevalence and being a leading cause of cancer death in the U.S.

What promising results were reported with OligoPhore™ technology?

Promising results include effective KRAS silencing and significant reduction in tumor growth in preclinical studies.

What is the NASDAQ ticker for Auris Medical?

The NASDAQ ticker for Auris Medical is EARS.