Small Fiber Neuropathy

– Rolling submission for suzetrigine moderate-to-severe acute pain NDA granted by FDA; first module submitted and on track to complete filing this quarter – – Successful completion of end-of-phase 2 FDA meeting for pain associated with diabetic peripheral neuropathy (DPN); Phase 3 program to initiate in 2H 2024 – – Breakthrough Therapy designation for pain associated with DPN granted by FDA – – Enrollment of Phase 2 study in patients with painful lumbosacral radiculopathy on track to complete by end of year – BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced important advancements across its suzetrigine pain program, which has the potential to be the first new class of medicine for acute and neuropathic pain in more than two decades. Suzetrigine is an oral selective NaV1.8 pain signal inhibitor (formerly known as VX-548). Following the positive Phase 3 results in acute pain announced in January 2024, the Food and Drug Administration (FDA) has granted a rolling New Drug Application (NDA) submission for suzetrigine in moderate-to-severe acute pain. Vertex has started the rolling submission process and is on track to complete the submission in the second quarter of 2024. Suzetrigine was previously granted FDA Fast Track and Breakthrough Therapy designations in moderate-to-severe acute pain. In neuropathic pain, Vertex released positive results from its Phase 2 study in December 2023 and recently completed a successful end-of-phase 2 meeting with the FDA. Vertex is now preparing to initiate a Phase 3 pivotal program of suzetrigine in patients with DPN in 2H 2024. In addition, the FDA recently granted suzetrigine Breakthrough Therapy designation for the treatment of pain associated with DPN. The Phase 3 program will include two identical 12-week randomized, double-blind, placebo-controlled studies evaluating the efficacy and safety of suzetrigine (70 mg once daily) in patients with DPN. The primary endpoint for both studies will be the change from baseline in weekly average of daily pain intensity on the numeric pain rating scale (NPRS) assessed at Week 12 compared to placebo. Both studies will also include a key secondary endpoint of change from baseline in the weekly average of daily pain intensity on the NPRS at Week 12 compared to pregabalin. Approximately 1,100 patients are expected to enroll in each Phase 3 study. After completing participation in the randomized controlled studies, patients may roll over into an open-label study to evaluate the long-term safety and effectiveness of suzetrigine in DPN. Additionally, Vertex continues to enroll its Phase 2 study of suzetrigine in patients with lumbosacral radiculopathy, or LSR, which is pain caused by impairment or injury to nerve roots in the area of the lumbar spine. The company is on track to complete enrollment in the Phase 2 LSR study by the end of the year. “Today marks a significant milestone on our journey to redefine the treatment of pain,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Given the favorable benefit/risk pro by suzetrigine across the entire clinical program and the positive interactions with regulators, we are excited by the opportunity to rapidly advance suzetrigine, a new non-opioid potential treatment, for the millions of patients suffering from acute and peripheral neuropathic pain.” Next Steps for the Pain Portfolio In line with its pain portfolio serial innovation strategy, Vertex continues to advance preclinical and clinical development of additional NaV1.8 and NaV1.7 pain signal inhibitors, for use alone or in combination, in acute and neuropathic pain. The company intends to advance its next generation NaV1.8 pain signal inhibitor VX-993 oral formulation into Phase 2 acute pain and peripheral neuropathic pain studies later this year. Vertex also anticipates initiating a Phase 1 study of an intravenous formulation of VX-993 later this year. About Acute Pain Acute pain is a disabling condition and is defined as pain lasting less than 3 months. It is estimated that over 80 million people are prescribed a medicine for acute pain every year in the U.S. Due to limited treatment options, there is an unmet need in acute pain management to improve the patient experience and reduce the economic and societal burden. About Peripheral Neuropathic Pain Peripheral neuropathic pain, or PNP, is a significant area of unmet need for patients suffering from pain. PNP is a collection of chronic conditions including pain associated with diabetic peripheral neuropathy (DPN), lumbosacral radiculopathy (LSR), small fiber neuropathy and trigeminal neuralgia. DPN and LSR are two of the largest segments within the estimated 10 million patients who are prescribed a medicine for PNP every year in the U.S. About Suzetrigine (VX-548) Suzetrigine (formerly VX-548) is an investigational oral, selective NaV1.8 pain signal inhibitor that is highly selective for NaV1.8 relative to other NaV channels. NaV1.8 is a voltage-gated sodium channel that plays a critical role in pain signaling in the peripheral nervous system. NaV1.8 is a genetically validated target for the treatment of pain, and suzetrigine has demonstrated a favorable benefit/risk pro three Phase 3 studies and two Phase 2 studies in moderate-to-severe acute pain. Suzetrigine also demonstrated positive results and a well-tolerated pro a Phase 2 study in patients with pain associated with diabetic peripheral neuropathy, a type of peripheral neuropathic pain. Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of pain signal inhibitors that have the potential to provide effective relief of pain without the limitations of currently available therapies, including the addictive potential of opioids. About Vertex Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency. Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X. Special Note Regarding Forward-Looking Statements This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements made by Carmen Bozic, M.D., in this press release, statements regarding Vertex’s expectations for the rolling submission to the FDA for suzetrigine in acute pain, including expectations to complete the submission in the second quarter of 2024, expectations to initiate the Phase 3 program of suzetrigine in patients with DPN in the second half of 2024, plans for the design of and enrollment expectations for the Phase 3 DPN program, plans to evaluate the long-term efficacy and safety of suzetrigine in patients with DPN, including enrollment expectations for this open-label study, and enrollment expectations for the Phase 2 study in LSR, including plans to complete enrollment in this study by the end of the year, our expectations for the anticipated benefits of suzetrigine, our plans to continue advancing additional NaV1.8 and NaV1.7 pain signal inhibitors in acute and neuropathic pain, our plans to advance VX-993 oral formulation into Phase 2 acute pain and PNP studies later this year, and our plans to initiate a Phase 1 study of an intravenous formulation of VX-993 later this year. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that our clinical studies for suzetrigine may be delayed, and that data from the company's research and development programs may not support registration or further development of its compounds due to safety, efficacy, and other risks listed under the heading “Risk Factors” in Vertex's annual report and in subsequent filings filed with the Securities and Exchange Commission and available through the company's website at and . You should not place undue reliance on these statements. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

FREEHOLD, N.J., April 09, 2024 (GLOBE NEWSWIRE) -- Chromocell Therapeutics Corporation (“Chromocell”, or the “Company”), (NYSE American: CHRO), a pioneer in the development of non-opioid pain treatment therapeutics, today announced that its Chief Executive Officer, Frank Knuettel, has issued the following letter to stockholders: Dear Fellow Stockholders, With my inaugural letter to stockholders, I am pleased to provide an update on our recent initial public offering (“IPO”), share our mission, outline the current status of our development programs, and discuss our growth and operational plans. We successfully closed our IPO on February 21, 2024, raising gross proceeds of approximately $6.6 million. Notably, almost all shares of common stock held by 5% holders, directors and officers of the Company prior to the IPO are subject to formal lock-up agreements. Additional key highlights since the close of the IPO include: All pre-IPO outstanding shares of Series A Convertible Preferred Stock (“Series A Preferred Stock”) were converted into shares of common stock at a price of $4.98 per share. All pre-IPO debt under our senior secured convertible notes, in the principal amount of approximately $587,000, was converted into shares of common stock at $4.80 per share. We transferred $2.2 million in liabilities to Chromocell Corporation in exchange for 2,600 shares of Series C Convertible Redeemable Preferred Stock (“Series C Preferred Stock”). The Series C Preferred Stock is the only remaining outstanding series of the Company’s preferred stock, has no dividend or voting rights and is convertible at a fixed price of $7.50 per share. Our CEO has agreed to further defer a considerable portion of his accrued compensation, affirming the belief in Chromocell’s mission. These and other actions the Company have taken since the close of the IPO have removed approximately $2.7 million of liabilities from the balance sheet. We expect that the net proceeds from our IPO will allow us to focus on accelerating the development of a portfolio of non-opioid pain treatments and related therapies. Opioids effectively treat pain, but their use often leads to serious side effects, including addiction and mortality. Despite the explosive growth of opioid addiction and the ongoing suffering of many patients, there has been a lack of new pain treatment therapies. We intend to build a robust pipeline of products to address several pain indications with molecules that show no addictive or euphoric properties. Our core development program targets the NaV1.7 sodium channel, as well as other receptors in the NaV family. NaV1.7 has been genetically validated as pain receptors in human physiology, and we have successfully conducted approximately animal models that demonstrated that blockage of NaV 1.7 channels showed significant pain reduction. We have formally launched two programs as follows:CC8464: Our lead compound to address certain types of neuropathic pain, CC8464, has completed Phase I safety trials. We conducted approximately ten (10) trials which demonstrated efficacy in a variety of different animal models as well as four Phase I trials involving approximately 200 patients. The Phase I results demonstrated no liver or renal toxicity, no central nervous system changes and no cardiovascular findings. With no central nervous system changes, patients did not report euphoric responses, indicating little likelihood of addictive properties and potential abuse. The only side effect experienced among these four studies was an incidence of rashes in about 4% of the patients exposed, which resolved in all cases with topical steroids and/or topical antihistamines (with the exception of one patient requiring systemic steroids). As a result, in discussions with the U.S. Food and Drug Administration (“FDA”), we plan to launch a slow dose escalation study to further evaluate the incidence of rashes. By titrating the dose over nine weeks, we anticipate that we will reduce or eliminate this side effect. We expect that the slow dose escalation study will also help determine the need for dose escalation in the final treatment regime. Even if it is ultimately determined that we will need an escalation period for chronic pain treatment therapy, which patients could well take for the remainder of their lives, we do not believe the dose escalation approach is consequential. Following the completion of the slow dose escalation study, we plan to commence a Phase II trial for the treatment of either of erythromelalgia (“EM”) or a Phase II trial for idiopathic small fiber neuropathy (“ISFN”). Both are orphan indications for which we plan to apply for orphan drug designations. The orphan indication may decrease the scope of the ultimate development program that is necessary for approval and is associated with a marketing exclusivity period from the FDA along with some tax advantages. The potential population for EM in the United States is estimated to be between 5,000 and 50,000 patients and the potential population for ISFN in the United States is estimated to be between 20,000 and 80,000 patients. In both instances, we expect patients would potentially take our drug for the remainder of their lives, and given the lack of good therapeutic alternatives, we expect to have a robust, ongoing, and durable market. CT2000: Our newly launched program is for the potential treatment of both acute and chronic eye pain. Current options for the treatment of ocular pain center on the use of corticosteroids and NSAID based therapeutics. These options suffer from sight-threatening complications such as Glaucoma and corneal melting, thus there is a large unmet need for other approaches. As an example of the potential patient population, we estimate that there are approximately 5 million cases of corneal abrasions per year in the United States. In addition, other potential indications associated with eye pain include: severe dry eye, side effects from photorefractive keratectomy (PRK) and pterygium surgery, Second eye cataract surgery, Neuropathic corneal pain Severe uveitis and severe iritis/scleritis. As the NaV1.7 receptor is present on the cornea and is a viable biological target for treating eye pain, we believe that we have a sound scientific basis for our ability to treat a multitude of eye pain indications. We have recently hired Dr. Simon Chandler, an expert with more than 30 years of experience in managing ophthalmic drug development programs and, notably, has gained FDA approvals in ocular pain indications. We are in the process of formulating CT2000 eye drops and expect to move into animal toxicity studies in the second half of 2024. From there, we intend to move into proof-of-concept studies in humans in Australia. Other Indications: We are exploring other exciting delivery methods and pain indications that we believe might considerably expand our target market in the pain treatment space. As a company, we have prioritized fiscal responsibility, operating leanly with four employees and utilizing consultants and CROs for additional work as needed. Additionally, we are availing ourselves of a significant 43.5% tax credit on clinical expenses by completing as much of our development work and trials in Australia as possible. We have launched a strategic initiative to secure non-dilutive, strategic capital options, including the potential out-licensing of, or entering into joint ventures for our proprietary drug compound for certain indications in certain markets. We believe that an increased focus on pain treatment therapeutics in the industry, combined with the need amongst generic producers for proprietary programs, make us an attractive candidate for this type of relationship. One final note with respect to our annal audit and the filing of our Annual Report on Form 10-K for the year ended December 31, 2023 (our “10-K”). The close of our IPO on February 21, 2024, in which our staff, auditors and lawyers were heavily engaged, was the sole cause of the delay in the filing of our 10-K by the prescribed due date. We do not expect any issues with filing our 10-K prior to the fifteenth day following the prescribed due date, as permitted by our filing of a Form NT with the SEC and SEC rules. Going forward, we plan to timely file our quarterly and annual reports for each reporting period. We truly feel that our IPO and recent therapeutic development activities have positioned Chromocell for long term growth and success. I wish to thank you for your support and remain a resource to each of you as we move forward. Sincerely,Frank Knuettel II CEO, Chromocell Forward-Looking Statements This press release contains forward-looking statements regarding the Company’s current expectations. These forward-looking statements include, without limitation, references to the Company’s expectations regarding (i) the initiation, timing, progress and results of preclinical and clinical trials for CC8464, CT2000 and other clinical programs, (ii) the timing, scope or results of regulatory filings and approvals, including timing of final FDA marketing and other regulatory approval of CC8464 and CT2000, (iii) the Company’s ability to achieve certain accelerated or orphan drug designations from the FDA, (iv) the Company’s estimates regarding the potential market opportunity for CC8464 and CT2000, (v) the Company’s plans and ability to successfully develop and commercialize compounds, (vi) the Company’s belief that its portfolio of therapeutics will be suitable for a multitude of eye pain indications, (vii) the Company’s belief that the market opportunity in under-served markets is considerable, (viii) the Company's intent to explore certain compounds for the treatment of pain indications, (ix) the Company's financial performance, (x) the impact of laws and regulations, (xi) the Company's ability to establish and maintain collaborations or obtain additional funding and (x) the anticipated use of net proceeds from the IPO. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ materially from those set forth in such forward-looking statements include, but are not limited to, risks and uncertainties related to (i) the Company expending its limited resources to pursue a compound or indication and failing to capitalize on different compounds or indications that may be more profitable or for which there is a greater likelihood of success and the Company potentially not being successful in discovering, developing and commercializing additional compounds, (ii) the Company needing to establish its market development capabilities to commercialize its products with the failure to do so potentially resulting in an inability to generate any revenue, (iii) the Company facing significant competition and its competitors potentially achieving regulatory approval before the Company or developing therapies that are more advanced or effective than the Company’s, which may adversely affect the Company’s financial condition, (iv) the Company’s ability to obtain and maintain adequate U.S. and foreign patent protection for its compounds, the Company facing litigation or administrative proceedings by a third-party over its patents, changes in U.S. or foreign patent law or interpretation thereof diminishing the value of its patents, and the Company’s ability to protect the confidentiality of its trade secrets, (v) third-parties instituting patent litigation against the Company in the U.S. or a foreign jurisdiction asserting that CC8464, CT2000 and/or additional compounds infringe its patent rights, the outcome of which would be uncertain and could have a material adverse effect on the success of the Company’s business, (vi) there being no guarantee that the results from prior clinical and preclinical studies will be indicative of the Company’s ability to complete studies or the results to be obtained in the current or future studies and clinical trials and (vii) the Company’s ability to retain key employees and scientific advisors and to attract, retain and motivate qualified personnel. These and other risks and uncertainties are described more fully in the section captioned “Risk Factors” in the Company’s Registration Statement on Form S-1 (SEC File No. 333-269188). Forward-looking statements contained in this announcement are made as of this date, and the Company undertakes no duty to update such information except as required under applicable law. Chromocell Media and Investor Inquires: LR Advisors LLC.Jason Assad678-570-6791Jason@Chromocell.com

Charles River will help bring NT-Z001 to the clinic by leveraging its off-the-shelf plasmid products, custom plasmid capabilities and adeno-associated virus (AAV) production. After charting multiple personalized medicine expansions in recent years, contract manufacturer Charles River Laboratories is back with another gene therapy pact—this time centered on an adeno-associated virus 9 (AAV9) candidate meant to serve as a non-opioid alternative for rare disease patients living with chronic pain. Charles River on Thursday announced a new accord with epigenetic gene therapy outfit Navega Therapeutics as part of the CDMO’s Cell and Gene Therapy Accelerator Program. The deal will grant Navega access to Charles River’s contract development and manufacturing capabilities and advisory services to produce the AAV gene therapy candidate NT-Z001 for phase 1 clinical trials, the companies said in a press release. Navega is positioning its gene therapy candidate to help treat chronic pain associated with rare diseases like small fiber neuropathy and primary erythromelalgia. The drug leverages Navega’s artificial intelligence-enabled zinc-finger gene-editing platform, the company explained. NT-Z001 specifically addresses a gain-of-function mutation in the Nav 1.7 gene, which is linked to inherited erythromelalgia, small fiber neuropathy and other chronic, debilitating pain disorders. Aside from pain tied to rare diseases, Navega figures its gene therapy could eventually address other pain indications, including neuropathic and inflammatory pain. Charles River, for its part, will help bring NT-Z001 to the clinic by leveraging its off-the-shelf plasmid products, custom plasmid capabilities and AAV production. Over the years, Charles River says it has significantly enhanced its cell and gene portfolio through a mix of acquisitions, capacity expansions and manufacturing platform launches, including eXpDNA for plasmids, nAAVigation for AAV and Lentivation for lentiviral vectors. Back in November 2022, the company debuted the expansion of its cell therapy manufacturing facility in Memphis, Tennessee. The plant reveal came just weeks after the CDMO opened a separate plasmid production facility in the U.K. Under the expansion, Charles River added nine processing suites to its 16 clean rooms at the Memphis site. The additions were designed to handle high-volume production—plus options for dual production lines—for late-stage clinical and commercial cell therapies, the company said at the time. Charles River also recently acquired a site in Rockville, Maryland, through its $350-million buyout of gene therapy CDMO Vigene Biosciences back in 2021. The site largely helps with the production of viral vectors, which have experienced supply constraints among advanced cell and gene therapies for several years. Elsewhere on the personalized medicines front, Charles River last year linked up with South Korea’s Rznomics to develop and crank out viral vectors for its partner’s experimental liver cancer gene therapy RZ-001. RZ-001 marks the first ribozyme-based RNA reprogramming approach to receive FDA authorization for evaluation in humans, the companies said last January.