RACK1

TORONTO, Ontario and CAMBRIDGE, Massachusetts, Jan. 08, 2024 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Issues Letter to ShareholderProMIS Neurosciences Inc. (Nasdaq: PMN), a biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today announced that its Chief Executive Officer, Neil Warma, issued the following letter to the Company’s shareholders. Dear ProMIS Shareholders, On behalf of the Board of Directors, I am honored to have recently joined the ProMIS management team as the interim CEO to steer the company through what we believe will be an exciting and informative clinical development path that could demonstrate the potential of ProMIS in the treatment of multiple dementias. Your steadfast support has been instrumental in our progress thus far, and I am excited to share some pivotal developments that will shape the future of our company. As part of our commitment to becoming a leader in the treatment of dementias, we are intensifying our focus on advancing our drug candidates into and through clinical development. Our ultimate goal is to get these potential new drugs to patients who are in desperate need of safe and effective treatment options. ProMIS’ scientific platform is truly unique. Designed and developed by our Chief Scientific Officer, Dr. Neil Cashman, MD, it leverages artificial intelligence (AI) to identify novel epitopes on toxic misfolded proteins, which have been shown to be an underlying cause of multiple diseases. Using a complex and proprietary algorithm, Dr. Cashman and the team at ProMIS are able to identify novel epitopes on misfolded proteins and design antibodies (drug candidates) that we believe will bind with high affinity to these targets, resulting in the elimination of these toxic and harmful proteins from the brain to prevent or slow disease progression. It is an elegant, yet complex solution that we believe is clearly differentiated among neurology-focused companies. The deliberate specificity of our antibodies is one unique aspect of our approach and we have been aggressive with our Intellectual Property strategy and have built a robust patent portfolio. Our belief is that if you can specifically target only the harmful or pathogenic proteins (i.e., misfolded proteins), this should result in a beneficial outcome to the patient and with fewer side effects. Our wealth of preclinical data demonstrates this, and we are hopeful the clinical data will continue to support this belief. I am pleased to share that our lead clinical drug candidate, PMN310, is progressing well through Phase 1a clinical development for the treatment of Alzheimer’s disease (AD). We recently received clearance from the Independent Data and Safety Monitoring Board to advance PMN310 to the second dose level in this Single Ascending Dose (SAD) trial in healthy volunteers. This milestone is a testament to the dedication and hard work of our clinical development team. We believe PMN310 holds immense promise to address the urgent need for effective treatments in AD and remains unique in its ability to specifically target only misfolded forms (i.e., toxic oligomers) of amyloid-beta (Aβ), which are believed to drive disease progression in AD. This specificity is expected to improve efficacy outcomes and prevent any off-target safety issues, which are common with other AD therapies currently marketed or in development. We remain committed to advancing PMN310 through the rigorous clinical development process. Over the coming months, we will be laser-focused on completing the SAD clinical study with PMN310 and, subsequently, rolling into the Phase 1b Multiple Ascending Dose (MAD) study, subject to the availability of sufficient capital. As the Phase 1b MAD study will be conducted in AD patients, this could provide the first signal demonstrating that PMN310 positively benefits patients with AD. We expect to report data on the Phase 1a study around mid-2024. This is our first drug candidate to advance into the clinic based on our novel and differentiated platform and should lead the way for others to follow. Beyond AD, we have our targets set on the treatment of amyotrophic lateral sclerosis (ALS), multiple system atrophy (MSA), and Parkinson’s disease. In line with our commitment to collaboration and growth, we are aggressively pursuing partnering discussions to leverage synergies and enhance our capabilities. We believe that strategic partnerships will not only accelerate our progress but also enable us to bring innovative treatments to patients more efficiently and could provide significant validation to the platform. We truly believe that we have a powerful technology platform from which multiple drug candidates could be developed and we are diligent in identifying ways to untap this potential while not distracting our focus from the lead development program with PMN310 and our tight control on cash management. Specific to our pipeline candidates, earlier this year, we presented data at key scientific conferences including validation of RACK1 as a potentially novel target for the treatment of ALS and frontotemporal lobar degeneration (FTLD-TDP). We remain excited about the early data generated for these debilitating diseases. In summary, I am honored to be representing you as ProMIS’ interim CEO. Our priorities are clear: to advance PMN310 through clinical development; to increase the Company’s visibility to better highlight the significant value of ProMIS; to advance strategic partnering discussions; and to effectively allocate and manage cash. We remain committed to our goal of generating shareholder value and improving the lives of patients worldwide. Finally, I want to express my deepest gratitude for your ongoing support as shareholders. Your belief in our mission and commitment to making a meaningful impact on the lives of those affected by neurodegenerative diseases drive us every day. Together, we are building a company that has the potential to treat multiple dementias and revolutionize the field in order to bring hope to millions of individuals and their families. As we navigate this transformative period, I am confident that ProMIS will emerge stronger, more resilient, and better positioned to make significant contributions to healthcare. We are on an exciting journey, and I look forward to sharing more successes with you in the future. Thank you for your continued trust and support. Sincerely, Neil WarmaChief Executive OfficerProMIS Neurosciences, Inc. About ProMIS Neurosciences Inc. ProMIS Neurosciences Inc. is a clinical stage biotechnology company focused on generating and developing antibody therapeutics selectively targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA). The Company’s proprietary target discovery engine applies a thermodynamic, computational discovery platform - ProMIS™ and Collective Coordinates - to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique approach, the Company is developing novel antibody therapeutics for AD, ALS and MSA. ProMIS has offices in Toronto, Ontario and Cambridge, Massachusetts. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Certain information in this news release constitutes forward-looking statements and forward-looking information (collectively, ‎‎“forward-looking information”) within the meaning of applicable securities laws. In some cases, but not necessarily in all cases, forward-looking information can be identified by the ‎use of forward-looking terminology such as “plans”, “excited to”, “targets”, “expects” or “does not expect”, “is expected”, “an opportunity exists”, ‎‎“is positioned”, “estimates”, “intends”, “assumes”, “anticipates” or “does not anticipate” or “believes”, or variations of such words and ‎phrases or state that certain actions, events or results “may”, “could”, “would”, “might”, “will” or “will be taken”, “occur” or “be ‎achieved”. In addition, any statements that refer to expectations, projections or other characterizations of future events or ‎circumstances contain forward-looking information. Specifically, this news release contains forward-looking information relating to the Company's planned timing for completion and anticipated data readout of the Phase 1a clinical trial and the anticipated use of proceeds from the private placement. Statements containing forward-looking information are not historical facts but instead represent management's current ‎expectations, estimates and projections regarding the future of our business, future plans, strategies, projections, anticipated events ‎and trends, the economy and other future conditions. Forward-looking information is necessarily based on a number of opinions, assumptions and estimates that, while considered reasonable by the Company as of the date of this news release, are subject to ‎known and unknown risks, uncertainties and assumptions and other factors that may cause the actual results, level of activity, ‎performance or achievements to be materially different from those expressed or implied by such forward-looking information, including, but not limited to, the Company’s ability to fund its operations and continue as a going concern, its accumulated deficit and the expectation for continued losses and future financial results. Important factors that could cause actual results to differ materially from those indicated in the forward-looking information include, among others, the factors discussed throughout the “Risk Factors” section of the Company's most recently filed annual information form available on www.SEDAR.com, in Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2022 and the section entitled “Risk Factors” in its Post-Effective Amendment No. 1 to Form S-1, filed March 17, 2023, each as filed with the Securities and Exchange Commission, and subsequent quarterly reports. Except as required by applicable securities laws, the Company undertakes no obligation to publicly update any forward-looking information, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. For further information: Visit us at www.promisneurosciences.com Please submit media inquiries to info@promisneurosciences.com. For Investor Relations: Stern Investor RelationsAnne Marie Field, Managing Directorannemarie.fields@sternir.comTel. 212-362-1200

Study results published in Acta Neuropathologica Communications support targeting of RACK1 as a potential therapeutic approach for Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). TORONTO, Ontario and CAMBRIDGE, Massachusetts, Dec. 20, 2023 (GLOBE NEWSWIRE) -- ProMIS Neurosciences Inc. (Nasdaq: PMN), a biotechnology company focused on the generation and development of antibody therapeutics targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), today announced a publication identifying Receptor for Activated C-Kinase 1 (RACK1) as a novel misfolded protein target for ALS and frontotemporal lobar degeneration (FTLD). The article published in the online edition of Acta Neuropathologica Communications is titled, "Targeting RACK1 to alleviate TDP-43 and FUS proteinopathy-mediated suppression of protein translation and neurodegeneration." “We are particularly pleased to have our data published in this well-regarded, peer-reviewed journal and contribute to the growing body of scientific knowledge on the pathogenic role of misfolded proteins in neurodegenerative diseases,” said Gail Farfel, Ph.D., Chief Executive Officer of ProMIS Neurosciences. “In addition, these data on RACK1 deliver another target for our pipeline as we advance clinical development of our lead product, PMN310, for Alzheimer’s disease.” TAR DNA-binding protein 43 (TDP-43) and Fused in Sarcoma/Translocated in Sarcoma (FUS) are ribonucleoproteins associated with pathogenesis of ALS and FTLD. Under normal conditions, TDP-43 and FUS are predominantly localized in the nucleus of cells, where they participate in the regulation of protein expression. In disease, however, they typically become mislocalized in the cytoplasm of neurons where they form aggregates. The study authors reported that pathological FUS and TDP-43 both co-aggregate with RACK1 resulting in suppression of protein synthesis. Importantly, they showed that removal (knock-down) of RACK1 can restore protein synthesis in a cell system and alleviate neurodegeneration in a fruit fly model of disease. “These study results provide an important contribution to our understanding of ALS/FTLD molecular pathology and continue to validate our approach of targeting misfolded proteins as a therapeutic strategy that translates across neurodegenerative diseases,” said Neil Cashman, M.D., Chief Scientific Officer and Co-founder of ProMIS. The complete article can be accessed online here. About ProMIS Neurosciences Inc. ProMIS Neurosciences Inc. is a clinical stage biotechnology company focused on generating and developing antibody therapeutics selectively targeting toxic misfolded proteins in neurodegenerative diseases such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA). The Company’s proprietary target discovery engine applies a thermodynamic, computational discovery platform - ProMIS™ and Collective Coordinates - to predict novel targets known as Disease Specific Epitopes on the molecular surface of misfolded proteins. Using this unique approach, the Company is developing novel antibody therapeutics for AD, ALS and MSA. ProMIS has offices in Toronto, Ontario and Cambridge, Massachusetts. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Certain information in this news release constitutes forward-looking statements and forward-looking information (collectively, ‎‎“forward-looking information”) within the meaning of applicable securities laws. In some cases, but not necessarily in all cases, forward-looking information can be identified by the ‎use of forward-looking terminology such as “plans”, “excited to”, “targets”, “expects” or “does not expect”, “is expected”, “an opportunity exists”, ‎‎“is positioned”, “estimates”, “intends”, “assumes”, “anticipates” or “does not anticipate” or “believes”, or variations of such words and ‎phrases or state that certain actions, events or results “may”, “could”, “would”, “might”, “will” or “will be taken”, “occur” or “be ‎achieved”. In addition, any statements that refer to expectations, projections or other characterizations of future events or ‎circumstances contain forward-looking information. Specifically, this news release contains forward-looking information relating to the Company's expectations regarding its clinical development of its lead product, PMN310, for Alzheimer’s disease. Statements containing forward-looking information are not historical facts but instead represent management's current ‎expectations, estimates and projections regarding the future of our business, future plans, strategies, projections, anticipated events ‎and trends, the economy and other future conditions. Forward-looking information is necessarily based on a number of opinions, assumptions and estimates that, while considered reasonable by the Company as of the date of this news release, are subject to ‎known and unknown risks, uncertainties and assumptions and other factors that may cause the actual results, level of activity, ‎performance or achievements to be materially different from those expressed or implied by such forward-looking information, including, but not limited to, the Company’s ability to fund its operations and continue as a going concern, its accumulated deficit and the expectation for continued losses and future financial results. Important factors that could cause actual results to differ materially from those indicated in the forward-looking information include, among others, the factors discussed throughout the “Risk Factors” section of the Company's most recently filed annual information form available on www.SEDAR.com, in Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2022 and the section entitled “Risk Factors” in its Post-Effective Amendment No. 1 to Form S-1, filed March 17, 2023, each as filed with the Securities and Exchange Commission, and subsequent quarterly reports. Except as required by applicable securities laws, the Company undertakes no obligation to publicly update any forward-looking information, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise. For further information: Visit us at www.promisneurosciences.com Please submit media inquiries to info@promisneurosciences.com. For Investor Relations, please contact: Stern Investor RelationsAnne Marie Fields, Managing Directorannemarie.fields@sternir.comTel. 212-362-1200

Fragile X syndrome, the most common form of inherited intellectual disability, may be unfolding in brain cells even before birth, despite typically going undiagnosed until age 3 or later. A new study showed that FMRP, a protein deficient in individuals with fragile X syndrome, has a role in the function of mitochondria, part of a cell that produces energy, during prenatal development. Fragile X syndrome, the most common form of inherited intellectual disability, may be unfolding in brain cells even before birth, despite typically going undiagnosed until age 3 or later. A new study published today in the journal Neuron by researchers at the University of Wisconsin-Madison showed that FMRP, a protein deficient in individuals with fragile X syndrome, has a role in the function of mitochondria, part of a cell that produces energy, during prenatal development. Their results fundamentally change how scientists understand the developmental origins of fragile X syndrome and suggest a potential treatment for brain cells damaged by the dysfunction. The study, led by four postdoctoral fellows -- Minjie Shen, Carissa Sirois, Yu (Kristy) Guo and Meng Li -- working in the lab of the lab of Xinyu Zhao, neuroscience professor and neurodevelopmental diseases researcher a UW-Madison's Waisman Center, found FMRP regulating a gene called RACK1 to promote mitochondrial function. Using a drug to enhance mitochondrial function, they were able to rescue brain cells damaged by lack of FMRP. Individuals with FXS may present developmental delays -- not sitting, walking or talking at expected ages -- as well as mild to severe intellectual disability, learning disabilities and social and behavioral problems. About half are also diagnosed with autism spectrum disorder. In previous research, Zhao found that mitochondria in mice with an FMRP deficiency that imitates FXS were smaller and unhealthy. Diving deeper, they also discovered that FMRP regulates genes involved in mitochondria fission-fusion, a process into which mitochondria fuse into a bigger shape in order to produce more energy for the cell. For the study, researchers grew brain cells called neurons grown from induced pluripotent stem cells. Because the stem cells came from people with FXS, the researchers could study the development of the disorder at a cellular level, determining whether mitochondria in human cells experienced issues similar to those in mice. "And indeed, we found that human neurons also have fragmented (smaller) mitochondria," Zhao says. They also found fewer mitochondria in neurons derived from FXS patients, which they did not see in the neurons of the mice modeling FXS. "In human neurons, it's a deficit in twofold. Not just fission-fusion, but also likely in the production of mitochondria," Zhao says. Although it has been long known that FMRP is deeply involved in FXS, the new discovery pinpoints a role for the protein in early development of the condition. Symptoms of FXS present long after the baby is born. Many babies appear to be developing typically before showing slower development, autistic features or developmental deficits. Children with FXS are typically diagnosed at three years of age or older. "Which means many scientists have been thinking that FMRP is more important for the postnatal maturation state," Zhao says. FMRP is protein that regulates the use of messenger RNA, sort of a of working copy of DNA used to produce the proteins that make things happen in cells. The researchers found that many of the mRNA strands that interact with FMRP are implicated in autism, providing a molecular link between FXS and autism spectrum disorder. Unexpectedly, many FMRP-bound mRNAs are expressed by genes classified as essential -- genes that are very busy during prenatal development but less active after birth. "This means that FMRP has a function in prenatal development that we have not really thought about before," Zhao says. "The fact that we found that FMRP also regulates prenatal development is really interesting and is actually indicating that what we see in fragile X syndrome, some of the effects already happened within the prenatal development." One of those essential genes is RACK1, identified for the first time as playing a role in FXS. "When RACK1 is lower in fragile X neurons, the mitochondria are suffering and the neurons exhibit mitochondrial deficit and hyperexcitability, like immature neurons. But when we reintroduce RACK1, we can rescue this," Zhao says. Using cultured neurons derived from individuals with FXS to screen for drugs, the researchers found a drug called leflunomide that corrected mitochondrial deficits. The treatment improved mitochondrial function and reduced the neurons' hyperexcitability. Next, Zhao wants to do a detailed biochemical analysis of mitochondrial dysfunction and figure out which key proteins are less present in FXS-affected neurons. She is also working on better understanding how RACK1 and leflunomide work to rescue mitochondrial function. Other collaborators on the study include Waisman Center investigators Qiang Chang, Anita Bhattacharyya, Andre Sousa, Daifeng Wang, Donna Werling and UW-Madison neuroscience professor Jon Levine. This research was supported by grants from the National Institutes of Health (R01MH118827, R01NS105200, R01MH116582, R01MH118827, R01HD064743, R01NS064025, R01AG067025, U01MH116492, P51 OD011106, U54HD090256, P50HD105353, R24HD000836 and T32 GM141013) and the Department of Defense (W81XWH-22-1-0621).