Lateral Meningocele Syndrome

5月15日，美国的Protara Therapeutics宣布，其1b期ADVANCED-1EXP扩展试验正在评估，该公司的研究性细胞疗法TARA-002，用于治疗患有原位癌(CIS)的高级别非肌肉浸润性膀胱癌(NMIBC)患者。第一批患者的给药是根据最近来自ADVANCED-1试验的1a期剂量递增部分的阳性初步数据。Protara首席医疗官Jathin Bandari医学博士说:“随着ADVANCED-1试验的积极初步结果，我们很高兴在ADVANCED-1EXP试验中给第一批患者用药。”“我们相信TARA-002有潜力在NMIBC治疗领域发挥有意义的作用，因为这种高度复发的疾病的治疗选择仍然有限。我们期待在NMIBC合并CIS患者中获得更多的TARA-002临床经验。”关于ADVANCED-1EXP该试验是一项1b期开放标签扩展试验，该试验以40KE1剂量评估12例CIS患者的膀胱TARA-002，包括卡介苗-naïve、卡介苗无反应和卡介苗治疗不足的患者。试验参与者将接受六次每周一次的TARA-002静脉滴注。该试验的主要目的是评估TARA-002的安全性、耐受性和抗肿瘤活性的体征，计划的主要终点是3个月的完全缓解(CR)率。在2023年4月的美国泌尿学会年会上，该公司宣布了TARA-002治疗高级别NMIBC患者的ADVANCED-1临床试验的1a期剂量递增部分的积极初步结果。临床数据表明，TARA-002总体耐受性良好，抗肿瘤活性显著，包括所有3例可评估的CIS患者的肿瘤消退，包括1例经过大量预处理的bcg无反应患者达到CR。基于这些结果，Protara计划启动ADVANCED-2，这是一项1b/2期开放标签试验，评估102例CIS患者的膀胱内TARA-002。1b期临床试验预计将招募27例CIS(±Ta/T1)、BCG-Naïve或BCG暴露患者，这些患者在CIS诊断前至少24个月未接受膀胱BCG治疗。该2期试验预计将招募75名bcg无反应CIS(±Ta/T1)患者。ADVANCED-2预计将于2023年下半年启动。关于TARA-002TARA-002是一种正在开发的用于治疗NMIBC和LMs的研究性细胞疗法，已被美国食品和药物管理局（FDA）授予罕见儿科疾病指定。TARA-002是从遗传上不同的A组的同一主细胞库开发的化脓性链球菌免疫增强剂日本销售。Protara已成功证明TARA-002和OK-432之间的生产可比性。当施用TARA-002时，囊肿或肿瘤内的先天性和适应性免疫细胞被激活并产生强大的免疫级联反应。中性粒细胞、单核细胞和淋巴细胞浸润异常细胞，免疫细胞分泌多种细胞因子，包括白细胞介素IL-2、IL-6、IL-8、IL-10、IL-12、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α，诱导强烈的炎症反应并破坏异常细胞。关于非肌肉浸润性膀胱癌NMIBC是指在膀胱内表面排列的组织中发现的癌症，尚未扩散到膀胱肌肉中。膀胱癌是美国第六大常见癌症，NMIBC约占膀胱癌诊断的6%。在美国，每年约有 80，65 名患者被诊断为 NMIBC。参考来源：1.https://www.biospace.com/article/releases/protara-therapeutics-announces-dosing-of-first-patients-in-phase-1b-advanced-1exp-trial-of-tara-002-in-nmibc-patients-with-carcinoma-in-situ/近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀ 点亮在看，传递信息♥

Favorable tolerability and anti-tumor activity observed in NMIBC patients treated with TARA-002 in ADVANCED-1 trial Company plans to initiate ADVANCED-2 trial in BCG-naïve CIS patients and BCG-unresponsive CIS patients in 2H23 Regulatory clearance received from FDA to commence Phase 2 trial of TARA-002 in Lymphatic Malformations; trial expected to initiate in Q423 Continue to expect cash, cash equivalents and investments of $90M as of March 31, 2023 to fund operations into 2025 NEW YORK, May 04, 2023 (GLOBE NEWSWIRE) -- Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, today announced financial results for the first quarter ended March 31, 2023 and provided a business update. “We are off to a strong start in 2023, notably with the recent presentation of positive preliminary data from the dose escalation portion of the ADVANCED-1 trial of TARA-002 in patients with high-grade non-muscle invasive bladder cancer (NMIBC) and expect to sustain this productive momentum in the months ahead,” said Jesse Shefferman, Chief Executive Officer of Protara Therapeutics. “Supported by these exciting preliminary findings, we are keenly focused on continued execution across the NMIBC program, including the recently announced Phase 1b/2 ADVANCED-2 trial of TARA-002 in patients with high-grade carcinoma in situ (CIS), which we expect to commence in the second half of this year. With final regulatory clearance from the U.S. Food and Drug Administration (FDA) on our Phase 2 trial in lymphatic malformations (LMs), we look forward to initiating STARBORN-1 in the near future and progressing our program to bring a much-needed therapy to these pediatric patients who have no approved treatments today. We remain committed to unlocking the full potential of TARA-002 and look forward to sharing our progress throughout the coming quarters.” Recent Highlights TARA-002 in NMIBC In April 2023 at the American Urological Association Annual Meeting, the Company announced positive preliminary results from the Phase 1a dose-escalation component of the ADVANCED-1 clinical trial of TARA-002, its investigational cell-based therapy, for the treatment of patients with high-grade NMIBC. The clinical data indicate that TARA-002 was generally well tolerated and anti-tumor activity was observed, including tumor regression in all three evaluable patients with CIS, including one heavily pre-treated Bacillus Calmette-Guérin (BCG)-unresponsive patient who achieved a complete response. The Company plans to initiate ADVANCED-2, a Phase 1b/2 open-label trial evaluating intravesical TARA-002 in up to 102 patients with high-grade CIS. The Phase 1b trial is expected to enroll 27 patients with CIS (± Ta/T1), BCG-Naïve or BCG-experienced, who have not received intravesical BCG for at least 24 months prior to CIS diagnosis. The Phase 2 trial is expected to enroll 75 patients with BCG-unresponsive CIS (± Ta/T1). ADVANCED-2 is expected to initiate in the second half of 2023. TARA-002 in Lymphatic Malformations (LMs) In April 2023, the Company received regulatory clearance from the FDA to commence STARBORN-1, a Phase 2 clinical trial of TARA-002 in pediatric patients with macrocystic and mixed-cystic LMs. Trial start-up activities are well underway in the ten pediatric centers of excellence participating in the trial, and initiation is expected in the fourth quarter of 2023. IV Choline Chloride in Intestinal Failure Associated Liver Disease (IFALD) Protara’s prospective study to enhance understanding of the incidence of IFALD in patients dependent on parenteral nutrition is ongoing, with results expected in the third quarter of 2023. The Company continues to engage with the FDA and plans to use both regulatory feedback and results from the prospective study to inform next steps for the IV Choline Chloride development program. First Quarter 2023 Financial Results As of March 31, 2023, cash, cash equivalents and restricted cash were $89.5 million. The Company expects its current cash and cash equivalents will be sufficient to fund its planned operations into 2025. Research and development (R&D) expenses for the first quarter of 2023 decreased to $5.1 million from $5.3 million during the first quarter of 2022. General and administrative expenses for the first quarter of 2023 decreased to $4.6 million from $5.6 million for the prior year period. This decrease was primarily due to decreases of $0.5 million in employee related expenses (including $0.3 million of stock-based compensation expense), $0.3 million resulting from a reduction in directors and officers liability insurance premiums, as well as $0.2 million related to a reduction in market development activities. For the first quarter of 2023, Protara reported a net loss of $9.0 million, or $0.80 per share, compared with a net loss of $10.8 million, or $0.96 per share, for the same period in 2022. Net loss for the first quarter of 2023 included approximately $1.6 million of stock-based compensation expenses. About TARA-002 TARA-002 is an investigational cell therapy in development for the treatment of NMIBC and of LMs for which it has been granted Rare Pediatric Disease Designation by the U.S. Food and Drug Administration. TARA-002 was developed from the same master cell bank of genetically distinct group A Streptococcus pyogenes as OK-432, a broad immunopotentiator marketed as Picibanil® in Japan and approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has successfully shown manufacturing comparability between TARA-002 and OK-432. When TARA-002 is administered, it is hypothesized that innate and adaptive immune cells within the cyst or tumor are activated and produce a strong immune cascade. Neutrophils, monocytes and lymphocytes infiltrate the abnormal cells and various cytokines, including interleukins IL-2, IL-6, IL-8, IL-10, IL-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha are secreted by immune cells to induce a strong inflammatory reaction and destroy the abnormal cells. About Non-Muscle Invasive Bladder Cancer (NMIBC) Bladder cancer is the 6th most common cancer in the United States, with NMIBC representing approximately 80% of bladder cancer diagnoses. Approximately 65,000 patients are diagnosed with NMIBC in the United States each year. NMIBC is cancer found in the tissue that lines the inner surface of the bladder that has not spread into the bladder muscle. About Lymphatic Malformations (LMs) LMs are rare, congenital malformations of lymphatic vessels resulting in the failure of these structures to connect or drain into the venous system. Most LMs are present in the head and neck region and are diagnosed in early childhood during the period of active lymphatic growth, with more than 50% detected at birth and 90% diagnosed before the age of 3 years. The most common morbidities and serious manifestations of the disease include compression of the upper aerodigestive tract, including airway obstruction requiring intubation and possible tracheostomy dependence; intralesional bleeding; impingement on critical structures, including nerves, vessels, lymphatics; recurrent infection, and cosmetic and other functional disabilities. About IV Choline Chloride and Intestinal Failure-associated Liver Disease (IFALD) IV Choline Chloride is an investigational, intravenous (IV) phospholipid substrate replacement therapy initially in development for patients receiving parenteral nutrition (PN) who have IFALD. Choline is a known important substrate for phospholipids that are critical for healthy liver function. Because PN patients cannot sufficiently absorb adequate levels of choline and no available PN formulations contain sufficient amounts of choline to correct this deficiency, PN patients often experience a prolonged progression to hepatic failure and death, with the only known intervention being a dual small bowel/liver transplant. If approved, IV Choline Chloride would be the first approved therapy for IFALD. It has been granted Orphan Drug Designations (ODDs) by the FDA for the treatment of IFALD and the prevention of choline deficiency in PN patients. About Protara Therapeutics, Inc. Protara is committed to advancing transformative therapies for people with cancer and rare diseases. Protara’s portfolio includes its lead program, TARA-002, an investigational cell-based therapy being developed for the treatment of non-muscle invasive bladder cancer and lymphatic malformations, and IV Choline Chloride, an investigational phospholipid substrate replacement for patients dependent on parenteral nutrition. For more information, visit . Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are "forward looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Protara may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “designed,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words or expressions referencing future events, conditions or circumstances that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such forward-looking statements include but are not limited to, statements regarding Protara’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Protara’s business strategy, including its development plans for its product candidates and plans regarding the timing or outcome of existing or future clinical trials; statements related to expectations regarding interactions with the FDA; Protara’s financial position; statements regarding the anticipated safety or efficacy of Protara’s product candidates; and Protara’s outlook for the remainder of the year. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that contribute to the uncertain nature of the forward-looking statements include: risks that Protara’s financial guidance may not be as expected, as well as risks and uncertainties associated with: Protara’s development programs, including the initiation and completion of non-clinical studies and clinical trials and the timing of required filings with the FDA and other regulatory agencies; general market conditions; changes in the competitive landscape; changes in Protara’s strategic and commercial plans; Protara’s ability to obtain sufficient financing to fund its strategic plans and commercialization efforts; having to use cash in ways or on timing other than expected;; the impact of market volatility on cash reserves; the loss of key members of management; the impact of general U.S. and foreign, economic, industry, market, regulatory, political or public health conditions; and the risks and uncertainties associated with Protara’s business and financial condition in general, including the risks and uncertainties described more fully under the caption “Risk Factors” and elsewhere in Protara's filings and reports with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. Protara undertakes no obligation to update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise, except as required by law. PROTARA THERAPEUTICS, INC. AND SUBSIDIARIES Condensed Consolidated Balance Sheets (in thousands, except share and per share data) As of March 31, 2023 December 31, 2022 Assets (unaudited) Current assets: Cash and cash equivalents $ 21,035 $ 24,127 Marketable debt securities 65,575 60,243 Prepaid expenses and other current assets 8,006 1,776 Total current assets 94,616 86,146 Restricted cash, non-current 745 745 Marketable debt securities, non-current 2,893 17,886 Property and equipment, net 1,521 1,592 Operating lease right-of-use asset 6,044 6,277 Other assets 586 644 Total assets $ 106,405 $ 113,290 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 4,081 $ 1,586 Accrued expenses 1,396 3,237 Operating lease liability 933 917 Total current liabilities 6,410 5,740 Operating lease liability, non-current 5,227 5,467 Total liabilities 11,637 11,207 Commitments and contingencies (Note 8) Stockholders’ Equity: Preferred stock, $0.001 par value, authorized 10,000,000 shares: Series 1 Convertible Preferred Stock, 8,028 shares authorized at March 31, 2023 and December 31, 2022, 8,027 shares issued and outstanding as of March 31, 2023 and December 31, 2022. - - Common stock, $0.001 par value, authorized 100,000,000 shares: Common stock, 11,306,753 and 11,267,389 shares issued and outstanding as of March 31, 2023 and December 31, 2022, respectively. 11 11 Additional paid-in capital 264,235 262,724 Accumulated deficit (169,009 ) (159,964 ) Accumulated other comprehensive income (loss) (469 ) (688 ) Total stockholders’ equity 94,768 102,083 Total liabilities and stockholders’ equity $ 106,405 $ 113,290 PROTARA THERAPEUTICS, INC. AND SUBSIDIARIES Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss (in thousands, except share and per share data) For the Three Months Ended March 31, 2023 2022 Operating expenses: Research and development $ 5,143 $ 5,269 General and administrative 4,589 5,605 Total operating expenses 9,732 10,874 Loss from operations (9,732 ) (10,874 ) Other income (expense), net: Interest and investment income 687 119 Other income (expense), net 687 119 Net loss (9,045 ) (10,755 ) Net loss per share attributable to common stockholders, basic and diluted $ (0.80 ) $ (0.96 ) Weighted-average shares outstanding, basic and diluted 11,303,869 11,250,127 Other comprehensive income (loss): Net unrealized (loss) gain on marketable debt securities 219 (731 ) Other comprehensive income (loss) 219 (731 ) Comprehensive Loss $ (8,826 ) $ (11,486 ) Company Contact: Justine O'Malley Protara Therapeutics Justine.OMalley@protaratx.com 646-817-2836

QTORIN™ rapamycin generally well-tolerated; no drug related severe adverse events and no observed rapamycin in systemic circulation 100% of participants were either “Much Improved” or “Very Much Improved” as rated by the Clinician Global Impression of Change following 12-weeks of QTORIN™ rapamycin End of Phase 2 meeting completed with U.S. Food and Drug Administration in February 2023; pending additional interactions with FDA, anticipate potential initiation of pivotal Phase 3 study in second half of 2023 FDA previously granted Fast Track Designation and Orphan Drug Designation to QTORIN™ rapamycin for Microcystic Lymphatic Malformations QTORIN™ rapamycin has potential to become first therapy and standard of care for the estimated more than 30,000 individuals with Microcystic Lymphatic Malformations in U.S., if approved WAYNE, Pa., March 09, 2023 (GLOBE NEWSWIRE) -- Palvella Therapeutics, Inc., a late clinical-stage biopharmaceutical company whose vision is to become the leading rare disease company focused on developing and commercializing novel therapies to treat individuals suffering from serious, rare genetic skin diseases for which there are no FDA-approved therapies, today announced positive topline results from the Company’s Phase 2 study of QTORIN™ rapamycin in Microcystic Lymphatic Malformations (Microcystic LM). Microcystic LM is a rare, chronically debilitating genetic disease caused by dysregulation of the PI3K/mTOR pathway. The disease is characterized by localized masses of malformed lymphatic vessels that protrude through the skin barrier and persistently leak lymph fluid (lymphorrhea) and bleed, often leading to recurrent serious infections and cellulitis. There are no FDA-approved treatments for the estimated more than 30,000 individuals living with Microcystic LM in the U.S. “People living with Microcystic LMs face daily challenges and frequent, sometimes life-threatening hospitalizations due to cellulitis. Current treatments are inadequate, invasive, and do not address the underlying mechanisms of this debilitating disease,” said James Treat, MD, a pediatric dermatologist at Children’s Hospital of Philadelphia and study investigator. “The encouraging results from the Phase 2 study of QTORIN™ rapamycin build upon the large, growing evidence base supporting targeted therapeutic intervention of Microcystic LMs via the mTOR pathway. We look forward to potentially initiating a pivotal Phase 3 study of QTORIN™ rapamycin in the second half of 2023, and to sharing the results from that study when they are available.” The proof-of-concept Phase 2, multi-center, open-label study featured multiple efficacy assessments, including clinician and patient global impression assessments as well as assessments of individual clinical manifestations that are important disease burdens for individuals living with Microcystic LM (lesion height, leaking, bleeding, erythema, and crusting/hyperkeratosis). Twelve individuals (n=12) with Microcystic LMs received QTORIN™ rapamycin once-daily for 12 weeks. Key findings from among the prespecified efficacy endpoints comparing end of treatment (Week 12) to the pre-treatment baseline period demonstrated improvements in several clinician and patient-reported outcomes: Efficacy Endpoints Week 12 Mean (n=12) Nominal, Two-sided p-value Clinician Global Impression of Change (CGI-C) 2.42 <0.0001 Clinician Global Impression of Severity (CGI-S) – Overall -1.33 <0.0001 • CGI-S Height -1.67 <0.0001 • CGI-S Leaking -0.92 0.0047 • CGI-S Bleeding -0.92 0.0197 • CGI-S Erythema -1.08 0.0016 • CGI-S Crusting/Hyperkeratosis -1.17 0.0012 Patient Global Impression of Change (PGI-C) 2.08 <0.0001 CGI-C and PGI-C improvements are represented by increases; CGI-S improvements are represented by reductions CGI-C and PGI-C are 7-points scales ranging from “Very Much Worse” (-3) to “Very Much Improved” (+3) CGI-S is a 5-point lesion severity scale p-values are nominal as there was no adjustment for multiplicity amongst efficacy endpoints All p-values from paired t-tests vs mean change of 0 as compared to baseline All twelve participants in the study demonstrated improvements on the PGI-C and CGI-C scales with all rated as either “Much Improved” or “Very Much Improved” by the clinicians after twelve weeks of treatment with QTORIN™ rapamycin. To help contextualize changes on efficacy endpoints and, specifically, better understand any patient quality of life impact resulting from QTORIN™ rapamycin, qualitative exit interviews were conducted by a third-party interviewer with a subset of participants from the Phase 2 study. In the study, QTORIN™ rapamycin was generally well-tolerated with the most common adverse events being application site pain and pruritus. No participants experienced drug related serious adverse events, and no unexpected adverse events occurred. No rapamycin was detected in the systemic circulation for all participants at all timepoints in the study. Palvella plans to present additional results of the Phase 2 study, including the results of the qualitative exit interviews, at an upcoming scientific meeting. Palvella completed an End of Phase 2 Meeting with the FDA in February 2023. Pending additional interactions with FDA, Palvella anticipates potentially initiating a pivotal Phase 3 study of QTORIN™ rapamycin in the second half of 2023. The FDA has granted Orphan Drug and Fast Track Designations to QTORIN™ rapamycin for the treatment of Microcystic LM. The European Medicines Agency (EMA) has also granted Orphan Drug Designation to QTORIN™ rapamycin for the treatment of microcystic LMs. About Palvella Therapeutics Founded and led by rare disease veterans, Palvella Therapeutics is a late clinical-stage biopharmaceutical company whose vision is to become the leading rare disease company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases in indications for which there are no FDA-approved therapies. Palvella’s development model involves partnering with patient advocacy organizations and their patient registries to design accelerated development programs aimed at expediting the introduction of targeted therapies to patients who currently lack any approved treatment options. We are developing a broad pipeline of product candidates based on our patented QTORIN™ platform, with an initial focus on serious, rare genetic skin diseases, many of which are lifelong in nature. Our lead product candidate, QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin) is currently in late-stage clinical development for Pachyonychia Congenita (PC), Microcystic Lymphatic Malformations (Microcystic LM), and the prevention of Basal Cell Carcinomas (BCCs) in Gorlin Syndrome (GS). QTORIN™ rapamycin has received FDA Fast Track Designation for PC, Microcystic LM, and for the prevention of BCCs in GS. QTORIN™ rapamycin is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency. The safety or efficacy has not been established for any use. James Treat, MD is a consultant for Palvella Therapeutics and a study investigator for the Phase 2 trial. Forward-Looking Statements This press release contains forward-looking statements concerning the development and commercialization of Palvella’s products, the potential benefits and attributes of such products, and the company’s expectations regarding its prospects. Forward-looking statements are subject to risks, assumptions and uncertainties that could cause actual future events or results to differ materially from such statements. These statements are made as of the date of this press release. Actual results may vary. Palvella undertakes no obligation to update any forward-looking statements for any reason. Contact information: Investors: Wesley H. Kaupinen Founder and CEO, Palvella Therapeutics wes.kaupinen@palvellatx.com Media: Marcy Nanus Managing Partner, Trilon Advisors, LLC mnanus@trilonadvisors.com