DSP

SAN DIEGO--(BUSINESS WIRE)-- Rejuvenate Bio, today announced new preclinical efficacy data for RJB-0402, a gene therapy targeting key disease-mediating pathways. RJB-0402 demonstrated efficacy in a mouse model of arrhythmogenic cardiomyopathy (ACM), an inherited disease caused by mutations in one of several genes encoding desmosomal proteins. A single dose of RJB-0402 was able to significantly improve cardiac function, preserve cardiac structure, and dramatically reduce premature ventricular contractions (PVCs) to normal levels. RJB-0402 was superior to gene replacement regarding its ability to normalize arrhythmias and demonstrated comparable effect on preservation of cardiac structure and function in this mouse model of ACM, which recapitulates human disease by disrupting the structure of the cardiac desmosome. Desmosomal proteins are essential for maintaining the integrity of cardiac muscle and individual muscle cells. Desmosomal protein mutations can disrupt the normal function of the heart and may result in life threatening heart rhythms and other cardiac issues, such as ACM, a rare and severe genetic heart condition that can be debilitating and life threatening. The current standard of care for patients with ACM consists of medications targeting arrhythmia management and heart failure, implantable cardioverter defibrillators (ICDs), and cardiac catheter ablations, none of which are curative. Even with optimal treatment, life-threatening arrhythmias and disease progression still occur, and can lead to heart failure. There are no disease-modifying treatments for ACM, other than cardiac transplant for late-stage disease. ACM therefore presents a profound unmet medical need for patients with the disease. “RJB-0402 shows exciting potential to be a significant breakthrough for patients suffering from this severe, life-limiting disease, who have an urgent need for better treatment options. If this approach proves effective to treat ACM, it would have a dramatic impact on the profound burden this disease has on patients and their families,” said Hugh Calkins, MD, Professor of Cardiology and Director of the Johns Hopkins Arrhythmia Service and the ARVD/C Program. “What makes RJB-0402 especially promising is its superior performance in the ACM nonclinical model, outperforming gene replacement therapies in reducing PVCs. Since RJB-0402 is not a mutation-specific gene therapy, this suggests that it has the potential to address all causes of ACM including those without known mutations, estimated to be 130,000 individuals, rather than being limited to a specific genetic subgroup, like gene replacement therapies,” said Daniel Oliver, CEO & Co-Founder, Rejuvenate Bio. “ARVC is a progressive genetic disorder that can affect multiple generations of family members. One of the first symptoms of ARVC can be sudden cardiac arrest, which can lead to sudden death. Therapies that are agnostic of the individual’s specific mutation are a vital avenue of investigation and we are thrilled to learn of Rejuvenate Bio’s continued progress in this area. This research gives much-needed hope to all families affected by ARVC,” said Alice Lara, President of the Sudden Arrhythmia Death Syndromes (SADS) Foundation. RJB-0402 is a liver-targeting adeno-associated virus vector-based gene therapy that drives over expression of FGF21. Since the doses required to overexpress FGF21 in the liver are meaningfully lower than those required for traditional AAV gene replacement therapies, this approach may have a beneficial effect on the safety pro the investigational product and could also dramatically reduce manufacturing costs. The initial clinical study for RJB-0402 will focus on patients with Desmoplakin-related arrhythmogenic cardiomyopathy (DSP ACM) at high risk of life-threatening ventricular arrhythmias and sudden cardiac death. “We see great promise for this therapy to treat this severe, life-threatening disease and improve the quality of life for patients with DSP ACM and look forward to engaging with the FDA in the near future to align on the requirements to initiate an IND,” said Deborah Ascheim, MD, Chief Medical Officer, Rejuvenate Bio. About Rejuvenate Bio Rejuvenate Bio is a gene therapy company focused on treating chronic disease based upon breakthrough technology developed at the Wyss Institute at Harvard University. Rejuvenate Bio utilizes gene therapy, proprietary targets, and tools to bring treatments to patients suffering from chronic conditions. The company is developing a pipeline of therapies with applications in cardiac and metabolic diseases. The company raised a Series A financing in 2021 led by Kendall Capital Partners, Digitalis Ventures, KdT Ventures and V Capital. Rejuvenate Bio is based in San Diego for more information, visit .

Researchers have identified a new mutation that leads to the cardiac disease arrhythmogenic cardiomyopathy (ACM). They assessed the effect of this mutation on heart muscle cells and obtained new insights into the underlying mechanism that causes the disease. The results of this study could contribute to the development of new treatments for ACM. Researchers from the group of Eva van Rooij in collaboration with the UMC Utrecht identified a new mutation that leads to the cardiac disease arrhythmogenic cardiomyopathy (ACM). They assessed the effect of this mutation on heart muscle cells and obtained new insights into the underlying mechanism that causes the disease. The results of this study, published on March 2nd in Stem Cell Reports, could contribute to the development of new treatments for ACM. Desmosomes Millions of heart muscle cells contract to let the heart fulfill its pumping function. To make sure these contractions are executed well, it is important that the individual heart muscle cells communicate with each other. Therefore, heart muscle cells have to be tightly connected with each other. In a healthy heart, these connections are made up of complex protein structures that form a bridge between the cells, so called desmosomes. When mutations occur in genes that contribute to these structures, this can lead to the development of arrhythmogenic cardiomyopathy (ACM). ACM is a progressive and often hereditary disease in which the heart fails to contract properly. Even though 1 in 5000 people develop ACM throughout life, a lot remains unknown about the disease and no effective treatment options exist to cure patients. Discovery of a new mutation "We investigated the genetic material of an ACM patient and encountered a previously unknown mutation in the gene desmoplakin," says first author of the study Sebastiaan van Kampen. Desmoplakin is one of the genes that is responsible for the formation of desmosomes. To investigate the role of this mutation in ACM onset, the researchers cultured heart muscle cells from the patient in the lab. Van Kampen: "We compared these heart muscle cells to the same heart muscle cells in which we repaired the mutation using CRISPR/Cas9. The heart muscle cells that contained the mutation turned out to be less tightly connected." In addition, the researchers discovered that these cells have fewer of ion channels. These channels are crucial for efficient propagation of the action potential, an electrical signal that stimulates contraction, between heart muscle cells. From this, they concluded that the new mutation can lead to ACM in patients. Underlying mechanism Multiple mutations are known to lead to ACM. Nevertheless, the underlying mechanism that leads to the disease remains largely unknown. To change this, the researchers used the cultured heart muscle cells from the patient as a model for the disease. They discovered that a protein named PITX2 is more highly expressed in the "diseased" heart muscle cells and that this protein is in part responsible for the loss of desmosomes and ion channels. "When we removed the protein from the diseased heart muscle cells, the levels of ion channels and desmosomal proteins in the cells of the patient showed a remarkable recovery," explains Van Kampen. The PITX2 protein thus plays an important role in the changes in the mutated heart muscle cells. Future treatments The study, published in Stem Cell Reports, can potentially contribute to the development of new treatments for ACM. Furthermore, the findings from this study offer new insights into the development of ACM that can be valuable for future research. "Although we don't know how the new mutation leads to increased levels of PITX2, we see the same happening in a second mutation. It's possible that increased levels of PITX2 lead to ACM in the context of many more mutations," says Eva van Rooij, group leader at the Hubrecht Institute and last author of the study. More research into these different mutations is therefore essential.

REN-001 IND submission planned for the second half of 2022 Data from pilot pig study showing successful cardiac transduction with REN-001 delivered via low-dose retrograde coronary sinus infusion published in Journal of the American College of Cardiology: Basic to Translational Science CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Renovacor, Inc. (NYSE: RCOR), a biotechnology company focused on delivering innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases, today reported financial results for the second quarter of 2022 and provided a corporate update. “The progress achieved at Renovacor this quarter enabled us to advance and expand our pipeline of precision AAV gene therapies that target the underlying drivers of devastating cardiovascular diseases,” said Magdalene Cook, M.D., Chief Executive Officer of Renovacor. “Peer-reviewed data published in the prestigious Journal of American College of Cardiology: Basic to Translational Science showed what we believe are meaningful levels of cardiac transduction when REN-001 was delivered locally to the heart of pigs at doses less than 1e13 vg/kg. We are now working to build upon these data with an expected IND submission for REN-001 in the second half of this year, and subsequent initiation of a Phase I/II clinical study in BAG3-DCM patients.” Dr. Cook continued, “In addition to the progress made with our lead candidate, we expanded our pipeline with a new research program, in collaboration with the University of Utah, targeting the three largest genetic segments of arrhythmogenic cardiomyopathy. ACM patients are in urgent need of therapies that can address the underlying biology of their debilitating disease, and we are thrilled to be collaborating with the University of Utah in these efforts. Looking ahead, we believe we are well-positioned with a pipeline of differentiated precision medicine programs and a strong team of experienced industry veterans at all levels of the company.” Second Quarter 2022 and Recent Highlights Continued Advancement of REN-001 Investigational New Drug (IND)-enabling Studies Supports Planned IND Submission in the Second Half of 2022: Planned IND submission is expected to enable the subsequent initiation of a Phase I/II clinical trial in BAG3-associated dilated cardiomyopathy (BAG3-DCM). Announced the Peer-reviewed Publication of Data from a Pilot Pig Study Showing Robust, Diffuse Cardiac Transduction with REN-001 Delivered via Low-dose Retrograde Coronary Sinus Infusion (RCSI): In the pilot study featured in a paper, which was published in Journal of the American College of Cardiology: Basic to Translational Science, low doses (<1e13 vector genome per kilogram) of REN-001 delivered locally to the heart of healthy Yucatan pigs using RCSI resulted in each cardiomyocyte containing, on average, at least one copy of the vector’s BAG3 payload (i.e., vector copy number threshold ≥1). Evaluation of cardiac tissue also showed diffuse transduction patterns across multiple regions of the heart and the presence of vector mRNA transcript. All evaluated animals tolerated the RCSI procedure without evidence of cardiac injury. Expanded Pipeline with New AAV Gene Therapy Research Program for Multiple Genetic Segments of Arrhythmogenic Cardiomyopathy (ACM): The program is being developed as a potential precision therapy for the three largest genetic segments of ACM: plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmoplakin (DSP) associated ACM. To accelerate this program, Renovacor entered into a research collaboration with the University of Utah’s Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI). The research program aims to restore gap junction protein trafficking and gap junction communication between heart muscle cells to treat life-threatening arrhythmias associated with ACM. The terms of the research agreement grant Renovacor an option for an exclusive license to inventions generated from research conducted under the collaboration. Second Quarter 2022 Financial Results Net loss for the three months ended June 30, 2022 was $4.0 million, or $0.23 per basic and diluted share, compared to net loss of $3.7 million, or $0.59 per basic and diluted share, for the same period in 2021. Excluding non-cash gains totaling $5.1 million for the three months ended June 30, 2022 related to the change in fair value of our warrant and share earnout liabilities, net loss was $9.1 million, or $0.52 per basic and diluted share. Research and development expenses were $6.3 million for the three months ended June 30, 2022, compared to $3.3 million for the same period in 2021. General and administrative expenses were $2.8 million for the three months ended June 30, 2022, compared to $0.4 million for the same period in 2021. Cash and cash equivalents as of June 30, 2022, totaled $62.0 million which, based on current projections, Renovacor believes will be sufficient to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2023. About Renovacor Renovacor is a biotechnology company focused on delivering innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases. The company’s lead program in BAG3-associated dilated cardiomyopathy (DCM) uses gene transfer technology to address the monogenic cause of this severe form of heart failure. Renovacor’s vision is to bring life-changing therapies to patients living with serious genetic cardiovascular and related diseases, by developing medicines that target the underlying cause of disease and provide a transformative benefit and significant improvement to quality of life. Forward-Looking Statements This press release contains certain forward-looking statements within the meaning of the “safe harbor” provisions of the United States Private Securities Litigation Reform Act of 1995, as amended, including statements regarding the anticipated development of Renovacor’s product candidates and development programs, clinical development timelines and financial outlook. These forward-looking statements generally are identified by the words “believe,” “project,” “expect,” “anticipate,” “estimate,” “intend,” “strategy,” “future,” “opportunity,” “plan,” “may,” “should,” “will,” “would,” “will be,” “will continue,” “will likely result,” and similar expressions. These forward-looking statements are based upon current estimates and assumptions of the Company and its management and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition, the ability of the company to grow and manage growth, maintain relationships with customers and suppliers and retain its management and key employees; the Company's ability to successfully advance its current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; the Company’s ability to submit an IND related to REN-001 on its anticipated timeline, and any challenges related to the clearance of such IND by the FDA; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility that the Company may be adversely affected by other economic, business or competitive factors, including inflationary pressures; the Company’s estimates of expenses and profitability; the evolution of the markets in which the Company competes; the ability of the Company to implement its strategic initiatives and continue to innovate its existing products; the ability of the Company to defend its intellectual property; the impact of the COVID-19 pandemic on the Company’s business, supply chain and labor force; and the risks and uncertainties described in the “Risk Factors” section of the Company's annual and quarterly and reports filed the Securities Exchange Commission. These filings identify and address important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and Renovacor assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Renovacor gives no assurance that it will achieve its expectations. Renovacor, Inc. Condensed Consolidated Statements of Operations (In thousands, except share and per share data) Three Months Ended Six Months Ended June 30, June 30, 2022 2021 2022 2021 Operating expenses: Research and development $ 6,289 $ 3,333 $ 12,219 $ 4,488 General and administrative 2,838 385 5,763 912 Loss from operations (9,127 ) (3,718 ) (17,982 ) (5,400 ) Other income (expense): Change in fair value of warrant liability 2,905 — 10,185 — Change in fair value of share earnout liability 2,152 — 10,318 — Other income (expense), net 46 — 49 — Net income (loss) $ (4,024 ) $ (3,718 ) $ 2,570 $ (5,400 ) Net income (loss) per share - basic and diluted $ (0.23 ) $ (0.59 ) $ 0.14 $ (0.86 ) Weighted-average number of common shares used in computing net income (loss) per share — Basic 17,478,008 6,274,566 17,471,341 6,274,566 — Diluted 17,478,008 6,274,566 17,550,126 6,274,566 Renovacor, Inc. Condensed Consolidated Balance Sheet Data (In thousands) June 30, December 31, 2022 2021 Cash and cash equivalents $ 61,993 $ 78,790 Other assets 2,729 2,209 Total assets $ 64,722 $ 80,999 Total liabilities $ 7,370 $ 27,455 Total stockholders’ equity 57,352 53,544 Total liabilities and stockholders’ equity $ 64,722 $ 80,999