BERWYN, Pa. / Aug 15, 2023 / Business Wire / Annovis Bio, Inc. (NYSE: ANVS), a late-stage clinical drug platform company developing transformative therapies to treat neurodegenerative diseases, including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) announced second quarter financial results for the period ended June 30, 2023, and reviewed recent accomplishments.

Second Quarter 2023 Highlights and New Developments

Clinical Updates

AD phase II/III study

• 52 sites have been activated and 201 patients have been screened through June 30: 61 patients have been enrolled to receive either one of three doses of buntanetap or placebo.
• This is a dose ranging trial of buntanetap (formerly known as posiphen or ANV401) in patients with mild to moderate Alzheimer’s Disease with a dosing treatment period of 12 weeks. Its mechanism of action, favorable toxicology profile, and oral mode of administration distinguish buntanetap as superior to other AD drugs. Other drugs attempt to remove just one neurotoxic protein and, at best, have a minor effect. Buntanetap has been shown to effectively stop the synthesis of four neurotoxic proteins -Amyloid Beta, Tau, alpha Synuclein, and TDP43 - the culprits behind nerve cell degeneration and death. Buntanetap’s early trials have shown its ability to reverse the destructive effects that Alzheimer’s Disease has on thinking and memory.

PD phase III study

• On June 3, Annovis announced it had reached full enrollment in the trial in a record nine months. Since the first patient was dosed in late August 2022, over 640 patients were screened and a total of 520 patients enrolled with 67 sites (43 in the United States and 24 in the European Union).
• The phase III trial is a randomized, double-blind, placebo-controlled trial investigating the efficacy, safety, and tolerability of buntanetap for early PD patients on top of their standard of care. By lowering levels of all the neurotoxic proteins, buntanetap improves axonal transport (the nerve cell’s information highway), which has been shown to be the cause of nerve cell degeneration and, ultimately, death.

• The record enrollment and low drop-out rate in this trial are believed to be due to the drug’s benefits demonstrated in the I/II trial:

  • It showed improvements in both body and motor function.
  • It is easily administered as a once daily pill.
  • It is safe and well-tolerated.

• The study is expected to conclude in November with top-line assessment data available by the end of the year.

• Annovis announced on June 20 the positive safety review by the Data and Safety Monitoring Board (DSMB) for its phase III trial of buntanetap for PD. The DSMB recommended that Annovis continue the trial as originally designed.

• The feedback from the DSMB included:

  • There were no drug-related SAEs (serious adverse events).
  • Each AE (adverse event) was less than 2 percent.
  • The dropout rate was 6 percent – significantly below expectations.
  • Patients enrolled well ahead of the expected timeline: 9 months to enroll 523 patients.

The planned enrollment has been achieved and based on this DSMB endorsement, Annovis expects topline results by the end of 2023.

Patents

• Annovis announced on June 27, 2023, the creation of a novel crystalline form of buntanetap (ANVS402) and the filing of a new composition of matter provisional patent with the U.S. Patent and Trademark Office. (ANVS402 is covered by a composition of matter claim as well as multiple claims for chronic and acute neurodegenerative diseases and for neuropsychiatric indications.)

• This composition of matter patent is a trailblazing patent for any pharmaceutical company developing a new drug; ANVS402 is the same essential drug as the previous form but offers structural advantages, including:
  • better stability
  • higher purity
  • longer half-life, improving buntanetap’s effectiveness.

• Approval of this patent will come with protection of ANVS402 and all its uses for a 20-year patent term. This significant time frame will enable Annovis to continue working on its robust pipeline, moving forward expeditiously toward developing novel drug therapies for many neurodegenerative diseases.

Financial Results (for the quarter ending June 30, 2023)

• Cash and cash equivalents were $15.7 million. Research and development expenses for the quarter were $8.2 million, compared to $4.0 million for the same period in 2022. The increase was primarily the result of an increase of $4.2 million in clinical expenses, as Annovis incurred costs related to its phase III study in early Parkinson’s Disease (PD) and its phase II/III Alzheimer's Disease (AD) study.
• General and administrative expenses for the second quarter were $1.5 million, compared to $1.9 million for the same period in 2022. The decrease was primarily the result of a decrease of $0.5 million in stock-based compensation expense, partially offset by an increase in salaries and professional fees of $0.1 million.
• Annovis reported a net loss of $9.5 million for the quarter, compared to a net loss of $5.9 million for the same period in 2022.

Staff News

New Employees

• In May, Annovis hired Sarah MacCallum as senior clinical project manager, bringing the total employee count to 10.

Annovis scientists spoke at events featuring novel approaches in neurodegenerative diseases with other leaders in the life sciences and pharmaceutical industries:

• Cheng Fang, Ph.D., Senior Vice President of Research and Development, hosted a roundtable discussion on “Emerging Non-Amyloid Targets for Alzheimer’s Disease” at the CNS Therapeutics Xchange-East Coast 2023 in Boston on May 24. She also presented a poster on buntanetap's novel target and mechanism of action for Alzheimer’s disease.
• Maria Maccecchini, Ph.D., CEO, was a member of a panel titled “Optimizing the Pipeline” at the Longwood Healthcare Leaders Spring MIT Conference, held June 7-8 at MIT’s Koch Institute in Cambridge.

• Annovis presented three posters at the Alzheimer’s Association International Conference (AAIC) 2023 annual meeting held in Amsterdam, Netherlands, from July 16-20.

  • Dr. Fang presented two posters: “Do Mouse Data Lie? For Buntanetap, They Totally Predict Human Outcome,” and “Interim Analysis Results of Buntanetap in Phase III Clinical Studies in Alzheimer’s and Parkinson’s Disease.
  • A third poster was presented by Don Elbert, Ph.D., associate professor of neurology, University of Washington School of Medicine, in collaboration with Annovis through the ongoing national Alzheimer’s Disease Cooperative Study (ADCS), titled “Stable Isotope Labelling Kinetics: Models and Methods to Evaluate APP Production Rates with Posiphen Treatment in the DISCOVER Clinical Trial.”
  • The posters’ combined findings tell the story of an exceptionally promising treatment for neurodegenerative diseases such as AD and PD.
    • First, in a mouse model of AD, buntanetap inhibits toxic proteins in the brain, improves axonal transport, lowers inflammation, and protects nerve cells from dying, all of which is associated with improved movement and cognition.
    • Second, these findings are also replicated in all the human AD and PD phase I and II trials to date.
    • Third, in both mice and humans, there is also evidence of a dose-response relationship between the drug dose administered and the inhibition of the neurotoxic proteins - important in determining the optimal dosage in future phase II and III trials.

Message from Dr. Maria

It is tremendously rewarding and important that our drug is safe, well-tolerated, and easily administered as a once-a-day pill. The two FDA-approved drugs for Alzheimer’s Disease require I.V. infusions and repeated brain imaging, and have well-documented, serious side effects that manifest as brain swelling or brain bleeding. As buntanetap continues to show significant progress through clinical trials, we remain on course and anticipate having topline data with good news to share before the end of the year.

The positive momentum we’re building with this drug is reflected in the more than 200% annual growth rate of our company over the last two years. The crystalline form of buntanetap will allow us to have a new 20-year patent protection for Annovis Bio to continue to move forward. There’s growing interest and excitement in the scientific and investment communities about our drug’s very real potential to not just alleviate devastating neurodegenerative disease symptoms but ultimately change the course of the diseases themselves.

–Maria L. Maccecchini, Ph.D., Annovis Founder, President, and CEO

About Buntanetap

Buntanetap (previously known as ANVS401 or posiphen) is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs), whose mode of action leads to a lower level of neurotoxic proteins and consequently less toxicity in the brain. In a Phase I/II clinical trial in AD and PD patients, buntanetap was shown to be well-tolerated and its pharmacokinetics were found to be in line with levels measured earlier in humans, meeting both the primary and secondary endpoints. Additionally, exploratory endpoints were also met, as treatment with buntanetap resulted in statistically significant improvement in motor function in PD patients and cognition in AD patients. Presently buntanetap is being studied in a phase III study in early PD patients and in a Phase II/III study in mild to moderate AD patients.

About Annovis Bio, Inc.

Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and other chronic neurodegenerative diseases. It is believed to be the only company developing a drug for both AD and PD designed to inhibit more than one neurotoxic protein to restore axonal and synaptic activity. By improving brain function, the company’s goal is to treat memory loss and dementia associated with AD as well as body and brain dysfunction associated with PD. Annovis conducted two phase I/II studies: one in AD patients and one in both AD and PD patients. In the AD/PD study buntanetap showed improvements in cognition in AD as well as movement and function in PD patients. For more information on Annovis Bio, please visit the Company's website www.annovisbio.com and follow us on LinkedIn, Facebook, Twitter and Threads.

Forward-Looking Statements

This press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The Company advises caution in reliance on forward-looking statements. Forward-looking statements include, without limitation, the Company's plans related to clinical trials. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially from those implied by forward-looking statements, including regarding patient enrollment, the effectiveness of buntanetap and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety and tolerability of buntanetap. See also additional risk factors set forth in the Company's periodic filings with the SEC, including, but not limited to, those risks and uncertainties listed in the section entitled "Risk Factors," in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC. All forward-looking statements in this press release are based on information available to the Company as of the date of this filing. The Company expressly disclaims any obligation to update or alter its forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law.