SYNGAP1

Three blockbuster-potential assets in late-stage clinical trials and four pivotal readouts expected in 2025; anticipate four commercial assets by 2028 Study 1 of Essential3 program for ulixacaltamide in essential tremor (ET) on track for Q1 2025 interim analysis; NDA filing for ulixacaltamide expected in 2025 Enrollment in EMBOLD study of relutrigine cohort 2 is on track; targeting NDA filing in 2026 Vormatrigine ENERGY program advancing with read-outs of RADIANT in first half of 2025 and POWER1 by year-end 2025 UCB has exercised its option to license KCNT1 small molecule candidate for global development and commercialization Cash and investments ~ $470 million at the end of 2024 support runway into 2028 BOSTON, Jan. 12, 2025 (GLOBE NEWSWIRE) -- Praxis Precision Medicines, Inc. (NASDAQ: PRAX), a clinical-stage biopharmaceutical company translating genetic insights into the development of therapies for central nervous system (CNS) disorders characterized by neuronal excitation-inhibition imbalance, today highlighted its portfolio progress and provided its business priorities for 2025. “2024 was a landmark year for Praxis with positive topline results from the Phase 2 photoparoxysmal response (PPR) trial of vormatrigine that led to initiating our ENERGY program in common epilepsies. Additional highlights this year were the unprecedented efficacy in cohort 1 of the EMBOLD study of relutrigine in developmental and epileptic encephalopathies (DEEs), followed by the initiation of the registrational cohort 2, and the continued overwhelming interest in the Essential3 program. Together, this progress has led to three blockbuster programs in late stage, with the potential for four product launches between 2026 and 2028,” said Marcio Souza, president and chief executive officer. Mr. Souza continued, “We are now well positioned for a readout-rich 2025, with results anticipated for ulixacaltamide in the Essential3 program in ET followed by our first NDA filing, as well as topline results for vormatrigine from the RADIANT study in focal onset seizures (FOS) and generalized epilepsy, and the POWER1 study in FOS. We are also thrilled to have received a third rare pediatric drug designation (RPDD) for relutrigine in Dravet Syndrome, and with strong interest in cohort 2 of the EMBOLD study, we expect to file the NDA in 2026. With regulatory feedback on the elsunersen program, we expect to initiate the pivotal trial in the first half of 2025. We are sufficiently funded to advance all programs through their topline readouts, with runway into 2028. We look forward to providing a thorough update across our portfolio at the planned Investor R&D Day in the second quarter of 2025.” Portfolio updates and anticipated milestones Cerebrum™ Small Molecule PlatformUlixacaltamide for Essential TremorET is an inadequately managed, undertreated and high burden disease with a prevalence of seven million patients in the U.S. The Essential3 program includes two Phase 3, registrational studies: Study 1 is a parallel design, placebo-controlled study (N=400) and Study 2 is a randomized withdrawal study (N=200). Since beginning recruitment in November 2023, over 100,000 patients have demonstrated interest in participating in the study. A pre-planned interim analysis of Study 1 is anticipated in the first quarter of 2025.At the time of the interim analysis update, Praxis will provide further detail on timing for the full readouts of Study 1 and Study 2.Praxis anticipates filing the NDA for ulixacaltamide in 2025.Following positive results from Essential3, the Company plans to re-initiate a study of ulixacaltamide in Parkinson’s disease, where there is significant and unmet need for non-dopaminergic treatment options. Vormatrigine (PRAX-628) for Common Epilepsies (Focal Onset Seizures and Generalized Epilepsy)An estimated 3.5 million people in the U.S. suffer from common epilepsies. Sodium channel therapy is the cornerstone of treatment for patients with epilepsy yet currently approved drugs have significant safety and efficacy limitations. Vormatrigine is the most potent sodium-channel modulator ever designed to precisely target the hyperexcitable state of sodium-channels in adult common epilepsies. In recently completed Phase 1 studies, vormatrigine continued to demonstrate an ideal profile with strong competitive differentiation. Full results will be shared at an upcoming medical conference and highlights include: Results from an additional 45 mg multiple ascending dose (MAD) cohort showed a dose proportional increase in exposure with excellent tolerability, similar to the 20 and 30 mg MAD cohorts completed previously.A Phase 1 food effect study demonstrated that food intake does not affect vormatrigine absorption and therefore there is no need to take vormatrigine with food, which increases flexibility in dosing and ease of use. Praxis continues to make progress on the ENERGY program to advance vormatrigine through efficacy and registrational trials. The EMPOWER observational study, in partnership with the Epilepsy Study Consortium, is aiming to better characterize seizure burden started enrolling patients in 2024 and has enrolled over 2,000 patients. Early results were shared during the Praxis scientific exhibit at the December 2024 American Epilepsy Society (AES) Annual Meeting. The RADIANT Phase 2 study for FOS and generalized epilepsy is currently enrolling patients, with topline results expected in the first half of 2025. RADIANT is an open-label study recruiting up to 50 patients with FOS or generalized epilepsy, who will be treated with a 30 mg dose over an 8-week period to evaluate the impact of vormatrigine on seizure burden.Enrollment for the POWER1 Phase 2/3 registrational study in patients with treatment resistant FOS is progressing as planned, with topline results anticipated in the second half of 2025. POWER1 is assessing adjunctive treatment, allowing dosing of vormatrigine on top of 1 to 3 antiseizure medications (ASMs), and aims to enroll approximately 250 patients in a parallel-arm study, comparing a treatment arm of 20 mg for 6 weeks followed by 30 mg for 6 weeks versus a placebo arm for 12 weeks.POWER2 will be the second registrational study for vormatrigine and is expected to begin enrollment in the second half of 2025 as a three-arm, 12-week study. Praxis continues to evaluate the potential for expansion of one of its highly functionally selective compounds into pain indications. The program will be discussed at Praxis’ planned R&D Day in the second quarter of 2025. Relutrigine (PRAX-562) for Developmental and Epileptic Encephalopathies DEEs cover a wide range of genetically and phenotypically defined epileptic conditions that are often characterized by onset of seizures at or shortly after birth and occur in approximately 200,000 patients in the U.S. Relutrigine is a sodium channel modulator with therapeutic potential across developmental epilepsies. Relutrigine is currently being evaluated in the EMBOLD study in SCN2A and SCN8A DEEs, with future plans for the EMERALD study in a broader, pan-DEE patient population. In cohort 1 of the EMBOLD study assessing relutrigine versus placebo in SCN2A gain-of-function (GoF) and SCN8A patients, relutrigine showed unparalleled results, with an update on the open-label extension (OLE) shared at the 2024 AES Annual Meeting . Key results included: 46% placebo-adjusted reduction in monthly motor seizures from baseline over a 16-week period.Patients continuing into the ongoing OLE (n=13) saw a 77% reduction in motor seizures from baseline through nine months of treatment.Over 30% of patients (n=5) achieved seizure freedom status while on relutrigine.Patients achieving seizure freedom had a median of 46 days of seizure freedom, inclusive of OLE period, compared to 3 days at baseline.Meaningful gains observed in alertness, communication and seizure severity suggest relutrigine has a disease modifying effect.Relutrigine was generally well-tolerated with no drug-related serious adverse events or dose reductions required. EMBOLD is currently enrolling 80 patients with SCN2A and SCN8A DEEs in registrational cohort 2, with topline results anticipated in the first half of 2026, to be followed by an NDA filing later in 2026.In December 2024, Praxis received RPDD for relutrigine for Dravet Syndrome. This is the third RPDD for relutrigine, in addition to SCN2A and SCN8A DEEs.Praxis remains on track to initiate the EMERALD registrational study in the first half of 2025.At the 2024 AES Annual Meeting, Praxis shared an update for an emergency use patient with extended benefit achieved after receiving relutrigine Solidus™ Antisense Oligonucleotide (ASO) PlatformElsunersen (PRAX-222) for early-seizure-onset SCN2A-DEE SCN2A GoF-DEE is a rare, genetic epilepsy characterized by early-onset and severe impact on development. The disease, as with all DEEs, affects not only the patient but also the entire caregiver ecosystem. In a Part 1 analysis of the EMBRAVE study, four patients receiving elsunersen over a four-month period achieved a 43% reduction in seizure burden compared to baseline. Praxis has completed discussions with global regulatory agencies to harmonize a registrational study design for elsunersen and will share the trial design and expected timelines in the first quarter of 2025.The second cohort of the EMBRAVE study continues to enroll patients in Brazil, evaluating safety and efficacy of elsunersen versus sham procedure.At the 2024 AES Annual Meeting, Praxis shared an update on four emergency access patients, including updates from the first-in-patient case who has received elsunersen for over 15 months. Additional Pipeline Updates In December 2024, UCB exercised its option to in-license global development and commercialization rights for a KCNT1 small molecule development candidate as part of the strategic research collaboration established in December 2022. Praxis has earned an option exercise fee and is eligible to receive future success-based development and commercialization milestone payments, for a total of up to approximately $100 million, in addition to tiered royalties on net sales of any resulting products from the collaboration.Praxis remains on track to nominate a development candidate for each of its early stage ASO therapeutic initiatives in 2025 PRAX-080: Focused on targeting PCDH19 mosaic expression which represents a pioneering approach to treating PCDH19-related epilepsy, a rare but devastating genetic disorder characterized by early-onset seizures and cognitive impairment, disproportionately affecting females.PRAX-090: Designed to address SYNGAP1 loss-of-function (LoF) mutations, a leading cause of severe intellectual disability and epilepsy in DEEs.PRAX-100: Targeting SCN2A LoF mutations, the predominant genetic link to de novo autism spectrum disorders (ASD). About UlixacaltamideUlixacaltamide is a differentiated and highly selective small molecule inhibitor of T-type calcium channels designed to block abnormal neuronal burst firing in the Cerebello-Thalamo-Cortical (CTC) circuit correlated with tremor activity. Ulixacaltamide, the most advanced program within Praxis’ Cerebrum™ small molecule platform, is currently in late-stage development for the treatment of essential tremor, Essential3 study. About Vormatrigine (PRAX-628)Vormatrigine is a next-generation, functionally selective small molecule targeting the hyperexcitable state of sodium-channels in the brain that is currently being developed as a once daily, oral treatment for adult focal onset seizures and generalized epilepsy. Preclinical data demonstrates vormatrigine is differentiated from standard of care, with the potential to be best-in-class for focal epilepsy. In vitro, vormatrigine has demonstrated superior selectivity for disease-state NaV channel hyperexcitability. In vivo studies of vormatrigine have demonstrated unprecedented potency in the maximal electroshock seizure (MES) model, a highly predictive translational model for efficacy in focal epilepsy. Data from the study demonstrated that vormatrigine can be safely dosed in healthy subjects to greater than 15 times the predicted human equivalent of the rodent MES EC50. To learn more about the POWER1 study please visit POWER1 study. About Relutrigine (PRAX-562)Relutrigine is a first-in-class small molecule in development for the treatment of developmental and epileptic encephalopathy (DEE) as a preferential inhibitor of persistent sodium current, shown to be a key driver of seizure symptoms in early onset SCN2A-DEE and SCN8A-DEE. Relutrigine’s mechanism of sodium channel blocking is consistent with superior selectivity for disease state sodium channel (NaV) channel hyperexcitability. In vivo studies of relutrigine have demonstrated dose-dependent inhibition of seizures up to complete control of seizure activity in SCN2A, SCN8A and other DEE mouse models. Relutrigine has been generally well-tolerated in three Phase 1 studies and has demonstrated biomarker changes indicative of NaV channel blocking effects. Relutrigine has received ODD and RPDD from the FDA, and ODD from the European Medicines Agency for the treatment of SCN2A-DEE and SCN8A-DEE and RPDD for Dravet Syndrome from the FDA. To learn more about the EMBOLD study, please visit EMBOLD study. About Elsunersen (PRAX-222)Elsunersen is an antisense oligonucleotide (ASO) designed to selectively decrease SCN2A gene expression, directly targeting the underlying cause of early-seizure-onset SCN2A-DEE to treat seizures and other symptoms in patients with gain-of-function SCN2A mutations. In vitro studies of elsunersen have demonstrated reduction in both SCN2A gene expression and protein levels. In vivo, elsunersen has demonstrated significant, dose-dependent reduction in seizures, improvement in behavioral and locomotor activity and increased survival in SCN2A mouse models, with potential to be the first disease-modifying treatment for SCN2A-DEE. Elsunersen has received ODD and RPD from the FDA, and ODD and PRIME designations from the European Medicines Agency for the treatment of SCN2A-DEE. The Elsunersen program is ongoing under a collaboration with Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), and RogCon, Inc. To learn more about the EMBRAVE study, please visit https://www.embravestudy.com/. About Praxis  Praxis Precision Medicines is a clinical-stage biopharmaceutical company translating insights from genetic epilepsies into the development of therapies for CNS disorders characterized by neuronal excitation-inhibition imbalance. Praxis is applying genetic insights to the discovery and development of therapies for rare and more prevalent neurological disorders through our proprietary small molecule platform, Cerebrum™, and antisense oligonucleotide (ASO) platform, Solidus™, using our understanding of shared biological targets and circuits in the brain. Praxis has established a diversified, multimodal CNS portfolio including multiple programs across movement disorders and epilepsy, with four clinical-stage product candidates. For more information, please visit www.praxismedicines.com and follow us on Facebook, LinkedIn and Twitter/X. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Praxis’ future expectations, plans and prospects, including, without limitation, statements regarding the anticipated timing of our clinical trials, the development of our product candidates and plans to initiate new clinical programs, the anticipated timing of regulatory submissions and interactions and our projected cash runway, as well as other statements containing the words “anticipate,” “believe,” “continue,” “could,” “endeavor,” “estimate,” “expect,” “anticipate,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “seek,” “should,” “target,” “will” or “would” and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in clinical trials; preliminary analyses from ongoing studies differing materially from final data from preclinical studies and completed clinical trials; the expected timing of clinical trials, data readouts and the results thereof, and submissions for regulatory approval or review by governmental authorities; regulatory approvals to conduct trials; and other risks concerning Praxis’ programs and operations as described in its Annual Report on Form 10-K for the year ended December 31, 2023 and other filings made with the Securities and Exchange Commission. Although Praxis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on information and factors currently known by Praxis. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Praxis undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.

Data from Single Ascending Dose (SAD) portion of Phase 1 study of CMP-CPS-001 for the treatment of urea cycle disorders (UCDs) demonstrates favorable safety resultsCompleted dosing in the first two Multiple Ascending Dose (MAD) cohorts, and initiated dosing in Cohort 3MAD safety and key study biomarker data expected in 2H 2025CAMP4 added to Russell 2000® IndexInitiation of new discovery program targeting a GBA1 regRNA for the treatment of Parkinson’s disease (PD)Company to present at the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15 at 3:45 p.m. PST CAMBRIDGE, Mass., Jan. 07, 2025 (GLOBE NEWSWIRE) -- CAMP4 Therapeutics Corporation (“CAMP4”) (Nasdaq: CAMP), a clinical-stage biotechnology company developing regRNA-targeting antisense oligonucleotide (ASO) therapies to upregulate gene expression to restore healthy protein levels, today provided corporate updates and key objectives for 2025. “2024 was a transformative year for CAMP4, highlighted by our successful IPO, and we are entering 2025 with tremendous momentum and a clear path towards delivering on our goals,” said Josh Mandel-Brehm, Chief Executive Officer of CAMP4. “We are very pleased with the clinical progress of our lead program CMP-CPS-001 for urea cycle disorders, which was granted Rare Pediatric Disease Designation and Orphan Drug Designation, validating the urgency of our novel regRNA-targeting ASOs. Additionally, our strategic partnership with BioMarin highlights confidence in our RAP platform. These achievements, combined with the proceeds from the IPO, position us to continue to progress our pipeline development and execute on key milestones this year.” “We are pleased to report the safety data from the SAD portion of our Phase 1 study of CMP-CPS-001 for UCDs, showing that the drug has been well-tolerated,” said Dr. Yuri Maricich, Chief Medical Officer of CAMP4. “We expect 2025 to be a pivotal year as we anticipate reporting MAD safety and key biomarker data in the second half of 2025. Results from these studies could enable us to advance the CMP-CPS-001 program into a registrational Phase 2/3 trial in 2026.” 2024 Key Highlights Completed IPO of 6,820,000 shares of common stock at an initial public offering price of $11.00 per share. Aggregate gross proceeds to CAMP4 were approximately $75.0 million. The underwriters also partially exercised their option to purchase an additional 643,762 shares of common stock for total offering gross proceeds of $82.1 million.Advanced Phase 1 clinical trial of CMP-CPS-001 for UCDs. The Phase 1 study is a randomized, double-blind, and placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of CMP-CPS-001 in 96 healthy volunteers.Completed planned interim analysis of all four SAD cohorts of the Phase 1 clinical trial of CMP-CPS-001 in 48 healthy volunteer participants. Safety results were favorable and consistent with the safety profile of approved liver-targeted ASOs, with all treatment emergent adverse events (TEAEs) being Grade 1 (mild) or Grade 2 (moderate). The two most common TEAEs across all cohorts were headache (six participants) and nausea (four participants). No safety trends of concern have been observed, and CMP-CPS-001 appears to be well-tolerated. Dosing is completed in the first two MAD cohorts, and the Safety Review Committee (SRC) has approved dose escalation to MAD Cohort 3, in which dosing has been initiated.The FDA granted Rare Pediatric Disease Designation and Orphan Drug Designation to CMP-CPS-001 for the treatment of UCDs.Entered strategic research collaboration agreement with BioMarin Pharmaceutical Inc., under which BioMarin has the right to select two targets identified by CAMP4’s RAP Platform to advance into clinical development.Company added to the Russell 2000® Index as part of the fourth quarter IPO additions.Appointed John Maraganore, Ph.D., and Rachel Meyers, Ph.D., as strategic advisors. Expected Milestones in 2025 MAD safety, pharmacokinetic and key pharmacodynamic biomarker data in healthy volunteers in the second half of 2025.GLP toxicity studies of lead ASO candidate for neurodevelopmental disorders caused by SYNGAP1 mutations to be initiated this year.Advance a new discovery program targeting a GBA1 regRNA to increase gene expression for the treatment of Parkinson’s disease (PD) caused by mutations in GBA1, with potential for application in sporadic PD.Company to focus on expanding its strategic partnerships to continue maximizing the value of its RAP platform. About CAMP4 Therapeutics CAMP4 is developing disease-modifying treatments for a broad range of rare and prevalent genetic diseases where increasing healthy protein levels may offer meaningful therapeutic benefits. Our approach allows for targeted gene upregulation by harnessing a fundamental mechanism of how genes are controlled. To increase gene expression, our therapeutic ASO drug candidates target regRNAs, which act locally on transcription factors and are the master regulators of gene expression. CAMP4’s proprietary RAP Platform™ enables the mapping of regRNAs and generation of therapeutic candidates designed to target the regRNAs associated with genes underlying haploinsufficient and recessive partial loss-of-function disorders, of which there are more than 1,200, in which a modest increase in protein expression may have the potential to be clinically meaningful. Learn more about us at www.CAMP4tx.com and follow us on LinkedIn and X. Forward-Looking Statements This press release contains forward-looking statements which involve risks, uncertainties and contingencies, many of which are beyond the control of the Company, which may cause actual results, performance, or achievements to differ materially from anticipated results, performance, or achievements. All statements other than statements of historical facts contained in this press release are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions, although not all forward-looking statements contain these words. Forward-looking statements include, but are not limited to, statements concerning CAMP4’s plans, objectives, expectations and intentions; the timing and results of ongoing and future clinical trials, including expectations on the timing of reporting MAD data from the CMP-CPS-001 trial and advancing the CMP-CPS-001 program into a registration-enabling trial; the timing to initiate GLP toxicity studies relating to CAMP4’s SYNGAP1 program; the timing to advance new discovery programs; its growth strategy; and cash runway guidance. The forward-looking statements in this press release speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions that could cause the Company’s actual results to differ materially from those anticipated in the forward-looking statements, including, but not limited to: the Company’s limited operating history, incurrence of substantial losses since the Company’s inception and anticipation of incurring substantial and increasing losses for the foreseeable future; the Company’s need for substantial additional financing to achieve the Company’s goals; the uncertainty of clinical development, which is lengthy and expensive, and characterized by uncertain outcomes, and risks related to additional costs or delays in completing, or failing to complete, the development and commercialization of the Company’s current product candidates or any future product candidates; delays or difficulties in the enrollment and dosing of patients in clinical trials; the impact of any significant adverse events or undesirable side effects caused by the Company’s product candidates; potential competition, including from large and specialty pharmaceutical and biotechnology companies; the Company’s ability to realize the benefits of the Company’s current or future collaborations or licensing arrangements and ability to successfully consummate future partnerships; the Company’s ability to obtain regulatory approval to commercialize any product candidate in the United States or any other jurisdiction, and the risk that any such approval may be for a more narrow indication than the Company seeks; the Company’s dependence on the services of the Company’s senior management and other clinical and scientific personnel, and the Company’s ability to retain these individuals or recruit additional management or clinical and scientific personnel; the Company’s ability to grow the Company’s organization, and manage the Company’s growth and expansion of the Company’s operations; risks related to the manufacturing of the Company’s product candidates, which is complex, and the risk that the Company’s third-party manufacturers may encounter difficulties in production; the Company’s ability to obtain and maintain sufficient intellectual property protection for the Company’s product candidates or any future product candidates the Company may develop; the Company’s reliance on third parties to conduct the Company’s preclinical studies and clinical trials; the Company’s compliance with the Company’s obligations under the licenses granted to the Company by others, for the rights to develop and commercialize the Company’s product candidates; risks related to the operations of the Company’s suppliers; and other risks and uncertainties described in the section “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as well as other information we file with the Securities and Exchange Commission. The forward-looking statements in this press release are inherently uncertain and are not guarantees of future events. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond the Company’s control, you should not unduly rely on these forward-looking statements. The events and circumstances reflected in the forward-looking statements may not be achieved or occur and actual future results, levels of activity, performance and events and circumstances could differ materially from those projected in the forward-looking statements. Moreover, the Company operates in an evolving environment. New risks and uncertainties may emerge from time to time, and management cannot predict all risks and uncertainties. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. Except as required by applicable law, the Company does not undertake to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contacts Investor Relations:Sandya von der WeidLifeSci Advisors svonderweid@lifesciadvisors.com Media:Jason Braco, Ph.D.LifeSci Communicationsjbraco@lifescicomms.com

Asthma patients have many drug options, but many patients find these choices either inconvenient or inadequate for severe cases of the chronic respiratory condition. Upstream Bio is pursuing a validated immunological target with a drug it contends offers dosing and efficacy advantages over a commercialized asthma medication from AstraZeneca and Amgen, and the biotech now has $225 million in IPO cash to help build its case with clinical data. Investors are persuaded by Upstream’s ambition, and their interest in the biotech’s new stock enabled the company to boost the deal size. After setting preliminary IPO terms of 12.5 million shares in the range of $15 to $17 each, which would have raised $200 million at the pricing midpoint, the Waltham, Massachusetts-based biotech on Thursday ended up offering 15 million shares at the top of the targeted price range. Upstream’s shares now trade on the Nasdaq under the stock symbol “UPB.” On Friday, Upstream’s first day on the public markets, the company’s stock price closed at $22, up 29.4% from the IPO price. Severe asthma is defined as disease that is uncontrolled despite treatment with high-dose inhaled corticosteroids. It can also be asthma that requires high-dosed inhaled corticosteroids to prevent symptoms from becoming uncontrolled. Biologic drugs offer patients an alternative treatment option for cases of uncontrolled asthma. Upstream’s lead drug is verekitug, a monoclonal antibody designed to block thymic stromal lymphopoietin, or TSLP. This signaling protein plays a role in immunological disorders and it’s upstream of multiple signaling cascades involved in many immune-mediated diseases, the company said in its IPO filing. presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB Of the six biologic drugs currently approved for severe asthma, only the AstraZeneca and Amgen product Tezspire addresses TSLP. But while Tezspire blocks the TSLP ligand, Upstream’s drug blocks the TSLP receptor. Upstream contends its approach could offer better control of asthma symptoms. It also offers potential for less frequent dosing. The company is testing dosing every 12 weeks and every 24 weeks — a much lower dosing burden compared to once monthly injections of Tezspire. “We believe that by reducing the frequency of dosing we can increase patient compliance with biologic treatments for severe asthma,” Upstream said in its IPO filing. “Additionally, a less frequent dose interval may appeal to patients that are not satisfied with their current treatment plan or are unwilling to take current biologics due to the treatment burden that comes with frequent dosing.” In Phase 1b testing, Upstream reported its drug led to “rapid and complete TSLP receptor occupancy.” Results also showed reductions in biological indicators of asthma that were sustained for up to 24 weeks after the last dose. Tezspire, which won FDA approval in 2021, was not part of this study as a comparator. But Upstream said verekitug’s results show it was about 300-fold more potent than the AstraZeneca and Amgen product based on published data for that drug. The Phase 1b results were presented in May during the American Thoracic Society International Conference. A Phase 2 test of verekitug in severe asthma began this past March; preliminary data are expected in the second half of 2026. Upstream’s approach to blocking TSLP has potential in other immunological conditions. A Phase 2 test in chronic rhinosinusitis with nasal polyps is expected to yield data in the second half of 2025. A separate mid-stage trial in chronic obstructive pulmonary disease (COPD) is expected to begin in the second half of next year. sponsored content Upcoming Webinar: Battle of the Budget: Employers vs. Rising Healthcare Costs Gain valuable knowledge and practical insights on how employers are addressing an increasingly complex healthcare budget landscape. By Personify Health Verekitug was discovered by Astellas Pharma, which advanced the drug candidate to Phase 1 testing. In 2021, months after Upstream formed, the young company acquired the Astellas asset for $81.1 million, according to the filing. There are no future payments owed to the Japanese pharma company. Upstream had raised $400 million from investors prior to the IPO, according to the filing. The company’s most recent financing was a $150 million Series B round announced in June and led by Enavate Sciences and Venrock Healthcare Capital Partners. Orbimed is Upstream’s largest shareholder with a 9.9% post-IPO stake, the filing shows. As of the end of June, the company reported its cash position was $235.8 million. Now that Upstream is public, the company plans to spend $150 million to continue the ongoing Phase 2 test of its lead program in severe asthma and advance it into Phase 3. About $40 million is budgeted for completing a Phase 2 test of the molecule in chronic rhinosinusitis with nasal polyps and starting a Phase 3 test in this indication. Another $50 million is set aside for costs associated with verekitug drug substance, including manufacturing. The company said it expects its capital will be sufficient to fund operations through mid-2027. CAMP4 Therapeutics Corrals $75M for Trials With a New Kind of RNA Therapy CAMP4 Therapeutics, a company named for the final camp before the summit of Mount Everest, has $75 million in IPO cash to continue development of treatments for haploinsufficiencies, disorders in which dysfunction in one copy of a gene leads to abnormally low levels of a key protein. The Cambridge, Massachusetts-based biotech aims to treat disease by targeting regulatory RNA, or regRNA, a type of RNA that regulates gene expression. The CAMP4 drugs are antisense oligonucleotides that bind to regRNA and get it to dial up gene expression. In a 2021 interview, CAMP4 CEO Josh Mandel-Brehm compared the approach to using a rheostat to adjust an electrical current. The company’s drugs, called RNA actuators, amplify gene expression in a controllable way, he said. Metabolic and central nervous system haploinsufficiencies are the company’s initial areas of focus. Lead program CMP-CPS-001 is in development for urea cycle disorders, inherited metabolic diseases that render the body unable to properly convert ammonia into urea. CAMP4’s drug is designed to amplify expression of an enzyme that catalyzes the first step of the urea cycle. In preclinical research, results showed a lowering of ammonia levels to normal ranges. A Phase 1 test is underway in healthy volunteers. Data from the single dose ascending portion of the trial are expected in the first quarter of 2025; the multiple ascending dose portion is expected to have data in the second half of next year. The next program in the pipeline is a preclinical treatment for SYNGAP1-related disorders, neurodevelopmental conditions caused by pathogenic variants in the SYNGAP1 gene. This haploinsufficiency leads to SYNGAP levels up to 50% below the normal range. CAMP4 had raised $183.3 million prior to its IPO. The company’s most recent financing was a $100 million Series B round in 2022 led by Enavate Sciences. Enavate is CAMP4’s largest shareholder with a 13.7% post-IPO stake, followed by 5AM Ventures with an 11.4% stake, the filing shows. As of the end of the second quarter of this year, CAMP4 reported a $12.6 million cash position. With the IPO proceeds, the company plans to spend $26 million to complete the Phase 1 test of its lead drug candidate for urea cycle disorders. About $18 million is set aside for continuing preclinical development of the SYNGAP1 program. Another $10 million is budgeted for expanding CAMP4’s platform technology and for development of other programs in the preclinical and discovery stages. CAMP4 was able to raise the money it needs for its plans, but it had to significantly cut its IPO price to do so. In preliminary IPO terms set earlier this week, CAMP4 planned to offer 5 million shares in the range of $14 and $16 each, which would have raised $75 million at the pricing midpoint. CAMP4 reached its $75 million goal by offering 6.82 million shares priced at $11 apiece. Those shares are trading on the Nasdaq under the stock symbol “CAMP.” CeriBell Upsizes IPO to Support a Commercialized EEG Tech Employing AI Medical technology company CeriBell raised $180.3 million to bolster commercialization efforts for its FDA-cleared electroencephalography (EEG) technology. The Ceribell System uses artificial intelligence to aid in the detection and management of seizures. The hardware is a disposable headband and a pocket-sized recorder that captures and wirelessly transmits EEG signals. An AI-powered seizure detection algorithm continuously monitors the patient’s EEG signal to detect seizures. Ceribell System, which is used in intensive care units and emergency departments, commercially launched in 2018. Sunnyvale, California-based CeriBell has two sources of recurring revenue: sales of the disposable headbands and a monthly subscription fee charged to the hospital customers that use the company’s technology. In 2023, CeriBell reported $45.2 million in total revenue, a 74% increase compared to the prior year. In the first half of this year, revenue was $29.7 million, a 45% increase compared to the same period in 2023. As of the end of September, CeriBell reported its cash position was $14 million. With the IPO proceeds, CeriBell plans to use $90 million for sales and marketing and $20 million for research and product development. CeriBell was able to upsize its IPO. In preliminary financial terms set earlier this week, the company estimated it would raise $88.9 million. The company revised those terms early Thursday, aiming to offer 6.7 million shares in the range of $16 to $17 each, which would have raised $174.9 million at the pricing midpoint. When the company finally priced its IPO late Thursday, it ended up offering 10.6 million shares priced at the top of the range. CeriBell’s shares trade on the Nasdaq under the stock symbol “CBLL.” Image: Jackie Niam, Getty Images