“We have already demonstrated and/or published in-vitro data indicating that Ampion™:
- decreases vascular permeability (an upstream event in inflammation),
- mobilizes and differentiates bone marrow-derived mesenchymal stem cells into normal chondrocytes,
- protects cells from apoptosis (programmed cell death) and autophagia,
- up-regulates both COX-2 mRNA and COX-2 protein in human synovial fibroblasts, human normal and osteoarthritic chondrocytes, and peripheral blood monocytes leading to increased production of the anti-inflammatory prostaglandins PGD2 and its metabolite 15-d-PGJ2,
- inhibits the differentiation of M0 macrophage into the M1 pro inflammatory macrophage phenotype,
- more unpublished data supporting the molecular changes that decrease OAK inflammatory damage and helps restore healthy chondrocytes and normal cartilage accretion.
“Because severe disease is associated with denudement of bone, MRI was used to quantitatively analyze and compute cartilage-covered and bare, denuded (no cartilage) bone areas for each opposing surface of the knee joint. Areas with exposed (denuded) bone were identified in the medial or lateral surface compartments of the knee. Some patients have disease predominantly in the medial compartment whereas others have more disease in the lateral compartment or more symmetrically. The open label study of 7 patients, each receiving 3 injections two weeks apart, that preceded the 40 patient STRUT study suggested that we should compare medial compartment disease and lateral compartment disease separately to appropriately matched placebo controls.”
Dr. Bar-Or continued: “A review of the quantitative MRI analysis of cartilage from the double-blind, three injections, vehicle controlled STRUT study (N=40) at 52 weeks compared to baseline was never published because the study was powered only to investigate the safety of the three injections of Ampion™ or saline at two week intervals. However, the MRI analysis after 52 weeks did provide some tantalizing results.
“A total of 37 patients had MRI data at baseline and at week 52. Of those, 20 patients had medial (n=10) or lateral disease (n=10) and the remaining (n=17) had either no denudement or symmetrical disease. Changes in cartilage thickness were examined across 6 anatomically defined sub regions, and patients with medial disease and lateral disease were analyzed separately.
“Among patients with medial disease, patients treated with Ampion™ had less cartilage thickness loss than patients treated with saline in all 6 medial sub regions. For instance, the mean cartilage thickness change over covered area of subchondral bone was -3μm for patients receiving Ampion™ and -34μm for patients receiving saline.
“Among patients with lateral disease, patients treated with Ampion™ had less cartilage loss than patients treated with saline in 5 of 6 lateral sub regions. Only Ampion™ patients showed increased cartilage thickness, in 2 lateral sub regions, as follows:
- Central part of the Lateral femorotibial compartment: +1μm for Ampion™ treated patients vs. -106μm for saline treated patients.
- Covered area of subchondral bone: +20μm for Ampion™ treated patients compared to -17μm for the saline group.
“We are encouraged by the results of the MRI analysis from the STRUT study. These results support those from the ‘in vitro’ work, and suggest Ampion™ does have the potential to provide a structure modifying/preserving therapy for osteoarthritis.”
Detailed results of the STRUT study were published as a feature article in the peer-reviewed journal Orthopedics in 2017: https://www.healio.com/orthopedics/journals/ortho/2017-1-40-1/%7B2ac26c9c-539c-4d93-b3a9-428849cd904e%7D/preliminary-trial-of-intra-articular-lmwf-5a-for-osteoarthritis-of-the-knee
Michael Macaluso, Ampio’s CEO stated: “This MRI analysis supports the anecdotal reports of prolonged pain and function relief, beyond 20 weeks we have received from patients with moderate to severe OAK treated with Ampion™. Ampio will perform larger studies to support a ‘disease modification or healing label,’ post marketing, possibly with more injections over a longer time period, in compliance with FDA recommendations should our BLA be accepted and approved. Additional information on these subjects is contained in the press releases below.”
Regulatory Exclusivity and IP protection:
The Company believes that Ampion™, a low molecular weight fraction of human serum albumin with anti-inflammatory properties, will be identified as a “reference product” upon FDA approval of their BLA. Reference products are granted twelve years of exclusivity under the PHS Act, 42 U.S.C. § 262(k)(7). Specifically, FDA is not permitted to approve an application for a biosimilar or interchangeable product until 12 years after the date of the first licensure of the reference product. The existing Ampion™ portfolio has patent coverage in all major jurisdictions throughout the world (U.S., Europe, Australia, Brazil, Canada, China, Eurasia, Hong Kong, India, Indonesia, Israel, Japan, Korea, Mexico, Malaysia, New Zealand, Philippines, Singapore, South Africa) for pharmaceutical compositions and methods of treating a range of conditions. The portfolio includes 125 issued patents and 85 pending applications throughout seven primary patent families having expiration dates that extend to 2035.
Osteoarthritis (OA) is a progressive disorder of the joints involving degradation of the intra-articular cartilage, joint lining, ligaments, and bone. The incidence of developing osteoarthritis of the knee over a lifetime is approximately 45%. As this disease is associated with age, obesity, and diabetes, this number will continue to grow. Certain risk factors in conjunction with natural wear and tear lead to the breakdown of cartilage. Osteoarthritis is caused by inflammation of the soft tissue and bony structures of the joint, which worsens over time and leads to progressive thinning of articular cartilage. Other symptoms include narrowing of the joint space, synovial membrane thickening, osteophyte formation and increased density of subchondral bone.
About Ampio Pharmaceuticals
Ampio Pharmaceuticals, Inc. is a development stage biopharmaceutical company primarily focused on the development of therapies to treat prevalent inflammatory conditions for which there are limited treatment options. We are developing compounds that decrease inflammation by (i) inhibiting specific pro-inflammatory compounds by affecting specific pathways at the protein expression and at the transcription level; (ii) activating specific phosphatase or depletion of the available phosphate needed for the inflammation process; and (iii) decreasing vascular permeability.
Ampio’s statements in this press release that are not historical fact, and that relate to future plans or events, are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by the use of words such as “believe,” “expect,” “plan,” “anticipate,” and similar expressions. These forward-looking statements include statements regarding Ampio’s expectations with respect to Ampion™, as well as those associated with clinical trials, expected results, regulatory approvals, the ability of Ampio to enter into partnering arrangements, the Biological License Application (BLA) and decisions and changes in business conditions and similar events, all of which are inherently subject to various risks and uncertainties. The risks and uncertainties involved include those detailed from time to time in Ampio’s filings with the Securities and Exchange Commission, including without limitation, under Ampio’s Annual Report on Form 10-K and other documents filed with the Securities and Exchange Commission. Ampio undertakes no obligation to revise or update these forward-looking statements, whether as a result of new information, future events or otherwise.
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