Third Quarter 2018 Results
ProMIS Neurosciences Inc. (TSE:PMN.TO) (OTC:ARFXF) has experienced a busy quarter since our previous report providing presentations and press releases addressing the:
‣ safety profile of PMN310 with respect to BAN2401 and aducanumab;
‣ the importance of selectivity against toxic oligomers; and
‣ the advancement of monoclonal antibody candidates targeting epitopes appearing on toxic oligomers for α-synuclein.
The company continued to advance its programs in the third quarter and expended $2.9 million1 in this endeavor. Research and development expenses were $1.9 million, up 42% compared to the prior year due to higher research program costs for the Alzheimer’s Disease program, greater recruiting expenses and higher costs to support its patent portfolio, partially offset by lower stock-based compensation. General and administrative expenses were $1.0 million in the period, rising 240% on higher consultant salaries and related costs, other professional fees, investor and public relations and stock-based compensation. No service or product revenues were generated for this preclinical company.
Cash stood at $4.7 million, declining $2.1 million sequentially. Cash burn in the quarter was ($2.4) million partially offset by $0.2 million of cash generated from warrant exercises. Current cash levels are expected to provide sufficient funding to support operations until 2Q:19.
ProMIS anticipates continued advancement of the Alzheimer’s Disease (AD) portfolio and PMN310 in preclinical development. Phase I clinical trial results for PMN310 are expected to be ready by 2020. Other programs are also targeted for advancement including Tau in AD, TDP43 and SOD1 in amyotrophic lateral sclerosis (ALS) and α-synuclein for Parkinson’s Disease (PD) as illustrated below in the company’s pipeline.
View Exhibit I – ProMIS Neurosciences Product Portfolio
Proposed Phase I Trial Design
ProMIS has provided some detail regarding its anticipated Phase I trial for PMN310; however, trial design remains in progress. There will be a strong emphasis on selecting useful biomarkers and several are being explored, especially ones that require a blood draw as opposed to cerebral spinal fluid. One biomarker in particular that has shown promise is Neurofilament Light Chain (NfL), which may be useful for measuring neuronal death. Neurofiliaments are byproducts of neuroaxonal breakdown and can indicate neurodegeneration. We anticipate results from the trial will will be available in 2020. In addition to measuring safety, the study will use validated biomarkers to measure dose dependent treatment effect. Low doses from 0.3 mg/kg to 1.0 mg/kg will be administered to healthy normal volunteers to identify any safety signals. As the trial progresses to higher doses, Alzheimer’s patients will be treated at various dose levels ranging from 3, 10, 20 and 40 mg/kg. We anticipate further detail as the trial approaches.
View Exhibit II – PMN310 Phase I Trial Design
In October, ProMIS announced a milestone related to the advance of its Parkinson’s Disease (PD) efforts. The company was able to identify monoclonal antibodies that will specifcially bind to α-synuclein toxic oligomers and detailed the discovery in a press release. We provided some background on ProMIS PD program and PD itself in an article highlighting α-synuclein, the stages of PD and the current paradigm that is applicable to the disease.
In July, ProMIS participated in the Alzheimer’s Association International Conference (AAIC) and presented a poster2 highlighting PMN310’s ability to bind to toxic oligomers. The poster provided several conclusions:
‣ humanized PMN310 provides better potency and safety as compared to other amyloid beta directed antibodies;
‣ PMN310’s key characteristics3 allow for greater safety at higher doses; and,
‣ greater selectivity can allow for a higher effective dose.
The following exhibit is taken from the poster and illustrates the binding response of humanized PMN310. ProMIS’ monoclonal antibody is compared to Biogen’s Phase III candidate aducanumab and Pfizer’s former Phase III and abandoned bapineuzumab.
View Exhibit III – Preferential Binding of PMN310 to Low Molecular Weight Fraction
In conjunction with the AAIC conference, ProMIS’ Chief Development Officer, Dr. Johanne Kaplan submitted a white paper and video presentation which we discuss here. Following the conference, ProMIS provided commentary on the key themes at the meeting.
On August 21 the company announced results demonstrating the lack of binding affinity between PMN310 and amyloid beta plaques. This result was compared to the binding of BAN2401 and aducanumab where robust amyloid beta plaque reactivity was observed. This result is important because it means that PMN310 is less likely to be diluted by plaque binding and greater amounts of the monoclonal antibody can target and bind to toxic oligomers. This targeted binding can also provide an improved safety profile by avoiding ARIA-E. Below are images of brain section exposed to PMN310 and other leading candidates for AD. Brown sections show the binding of antibodies to plaques in the brain. Absence of this stain indicates the desired lack of binding to inert plaques.
View Exhibit IV – mAb Binding to Amyloid β Plaques
ProMIS has continued to move forward with its preclinical PMN310 work and is expected to advance its IND-enabling work and identify relevant biomarkers for its clnical trials. Parallel with these efforts is continued interaction with the scientific, investment and corporate community to present the promise of PMN310 and other pipeline candidates to garner KOL support, financing and partnerships. We believe ProMIS represents an attractive opportunity to gain exposure to an immense disease area with no other approved therapies. There are almost six million persons with AD in the US and over 30 million outside of the US that suffer from the disease. Additionally, there is a larger population with MCI and pre-Alzheimer’s which may benefit even more from toxic oligomer sequestering therapy. The path forward is relatively clear with other assets including aducanumab setting the precedent for trial design.
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1 Currency is denominated in Canadian Dollars
2 The poster by Kaplan (et al.), is entitled Humanized PMN310 shows enhanced therapeutic potential by binding toxic low molecular weight Aβ oligomers while avoiding ARIA-related binding to Aβ deposits in AD patient brains.
3 Key characteristics of PMN310 include no binding to amyloid beta plaques and the use of the IgG4 isotype, which limit the incidence of amyloid-related imaging abnormalities (ARIA) edema or brain swelling.