Antolimab

SAN CARLOS, Calif., March 14, 2024 (GLOBE NEWSWIRE) -- Allakos Inc. (the “Company”) (Nasdaq: ALLK), a biotechnology company developing antibodies for the treatment of allergic, inflammatory and proliferative diseases, today provided a business update and reported financial results for the fourth quarter and full year ended December 31, 2023. Recent Allakos Events Completed dosing in the single ascending dose (SAD) cohorts and continued dosing in the multiple ascending dose (MAD) cohorts of the randomized, double-blind, placebo-controlled Phase 1 trial of Intravenous (IV) AK006 in healthy volunteers.Initiated the randomized, double-blind, placebo-controlled subcutaneous (SC) AK006 cohort in healthy volunteers.Published preclinical research in Allergy showing that AK006 controls mast cell function through interaction with multiple activating receptors and key signaling pathways.Presented preclinical data at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2024 highlighting AK006’s mechanism of action and ability to reduce MRGPRX2-induced skin inflammation.Reported topline data from the Phase 2 study of SC lirentelimab in patients with atopic dermatitis and Phase 2b study of SC lirentelimab in patients with chronic spontaneous urticaria.Halted lirentelimab-related development activities and announced a restructuring plan to reduce costs and focus on AK006 clinical development. As a result of the restructuring, Allakos expects its cash runway to extend into mid-2026. Upcoming Allakos Anticipated Milestones Report safety, pharmacokinetics (PK), and pharmacodynamic (PD) results from the Phase 1 trial of IV AK006 in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples in Q2 2024.Initiate the randomized, double-blind, placebo-controlled Phase 1 trial of IV AK006 in patients with chronic spontaneous urticaria in Q2 2024.Report safety, PK, and PD results from the Phase 1 trial of SC AK006 in healthy volunteers, including data to confirm Siglec-6 receptor occupancy in skin biopsy samples in Q3 2024.Report topline data from the Phase 1 trial of IV AK006 in patients with CSU at year end 2024 Cash Guidance The Company expects that the restructuring activities will extend the cash runway into mid-2026. The Company ended the fourth quarter of 2023 with approximately $170.8 million in cash, cash equivalents and investments. The Company’s outlook for 2024 cash, cash equivalents and investments is as follows: Cash, cash equivalents and investments at year end 2023$171 millionEstimated 2024 net cash used in operating activities (GAAP)($85 to $90 million)Estimated cash, cash equivalents and investments at year end 2024$81 to $86 million Components of estimated 2024 net cash used in operating activities for the year ended December 31, 2024 are as follows: Estimated net cash used in operating activities (GAAP)$85 to $90 millionLess: estimated lirentelimab closeout, severance and other costs 1($30 million)Estimated adjusted net cash used in operating activities (non-GAAP) 2$55 to $60 million 1 The Company anticipates that the significant majority of the restructuring expenditures, including approximately $4 million of severance, will be paid in the first half of 2024. 2 For additional information on the Company’s use of non-GAAP financial information, please see the section titled “Non-GAAP Financial Measure” below. Fourth Quarter 2023 Financial Results Research and development expenses were $53.8 million in the fourth quarter of 2023 compared to $35.4 million in the fourth quarter of 2022, an increase of $18.4 million. This quarter over quarter increase is attributed to $15.0 million of increased manufacturing costs and $3.4 million of increased other research and development expenses related primarily to our clinical studies. General and administrative expenses were $11.2 million for the fourth quarter of 2023 compared to $10.8 million for the fourth quarter of 2022, an increase of $0.4 million. The quarter over quarter change included $0.3 million of increase stock-based compensation expenses and $0.1 million increase in other general and administrative expenses. Allakos reported a net loss of $62.6 million in the fourth quarter of 2023 compared to $43.0 million in the fourth quarter of 2022. The fourth quarter of 2023 included noncash expenses for stock-based compensation of $10.2 million, compared to $9.3 million in the same period in 2023, and depreciation expense of $1.5 million in each of the fourth quarters of 2023 and 2022. Net loss per basic and diluted share was $0.71 for the fourth quarter of 2023 compared to $0.50 in the fourth quarter of 2022. Allakos ended the fourth quarter of 2023 with $170.8 million in cash, cash equivalents and investments resulting in a net decrease in cash, cash equivalents and investments of $23.1 million during the fourth quarter of 2023. About Allakos Allakos is a clinical stage biotechnology company developing therapeutics that target immunomodulatory receptors present on immune effector cells involved in allergy, inflammatory and proliferative diseases. Activating these immunomodulatory receptors allows for the direct targeting of cells involved in disease pathogenesis and, in the setting of allergy and inflammation, has the potential to result in broad inhibition of inflammatory cells. The Company’s most advanced product candidate is AK006. AK006 targets Siglec-6, an inhibitory receptor expressed on mast cells. Mast cells are widely distributed in the body and play a central role in the inflammatory response. Inappropriately activated mast cells have been identified as key drivers in a number of severe diseases affecting the gastrointestinal tract, eyes, skin, lungs and other organs. In preclinical studies, AK006 appears to provide deep mast cell inhibition and, in addition to its inhibitory activity, reduce mast cell numbers. For more information, please visit the Company’s website at www.allakos.com. Non-GAAP Financial Measure In this press release, Allakos’ estimated net cash used in operating activities is provided in accordance with generally accepted accounting principles (GAAP) in the United States and also on a non-GAAP basis. Non-GAAP estimated adjusted net cash used in operating activities excludes estimated lirentelimab closeout, severance and other costs. Non-GAAP estimated adjusted net cash used in operating activities is provided as a complement to estimated net cash used in operating activities provided in accordance with GAAP because management believes the non-GAAP financial measure is useful to investors in assessing the Company’s operating performance. Management also uses the non-GAAP financial measure to establish operational goals that are communicated internally and externally, to manage the Company’s business and to evaluate its performance. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such forward-looking statements include, but are not limited to, Allakos’ progress, business plans and areas of focus; the expected timing of reporting data from its clinical trial of AK006; the clinical potential of AK006; and Allakos’ anticipated clinical milestones. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to: Allakos’ stages of clinical drug development; Allakos’ ability to timely initiate and complete clinical trials for AK006; Allakos’ ability to obtain required regulatory approvals for its clinical trials; uncertainties related to the enrollment of patients in its clinical trials; Allakos’ ability to demonstrate sufficient safety and efficacy of its product candidates in its clinical trials; uncertainties related to the success of clinical trials, regardless of the outcomes of preclinical testing or early-stage trials; Allakos’ ability to obtain regulatory approvals to market its product candidates; market acceptance of Allakos’ product candidates; uncertainties related to the projections of the size of patient populations suffering from the diseases Allakos is targeting; Allakos’ ability to advance additional product candidates beyond AK006; uncertainties related to Allakos’ ability to realize the contemplated benefits of its restructuring and related reduction in force; Allakos’ ability to accurately forecast financial results; Allakos’ ability to obtain additional capital to finance its operations, research and drug development; general economic and market conditions, both domestic and international; domestic and international regulatory obligations; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in documents that Allakos files from time to time to with the SEC. These documents contain and identify important factors that could cause the actual results for Allakos to differ materially from those contained in Allakos’ forward-looking statements. Any forward-looking statements contained in this press release speak only as of the date hereof, and Allakos specifically disclaims any obligation to update any forward-looking statement, except as required by law. These forward-looking statements should not be relied upon as representing Allakos’ views as of any date subsequent to the date of this press release. Source: Allakos Inc. Investor Contact:Adam Tomasi, PresidentAlex Schwartz, VP Strategic Finance and Investor Relationsir@allakos.com Media Contact:Denise Powelldenise@redhousecomms.com ALLAKOS INC. UNAUDITED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except per share data) Three Months Ended Twelve Months Ended December 31, December 31, 2023 2022 2023 2022 Operating expenses Research and development $53,801 $35,388 $150,908 $265,081 General and administrative 11,182 10,828 45,148 57,348 Total operating expenses 64,983 46,216 196,056 322,429 Loss from operations (64,983) (46,216) (196,056) (322,429)Interest income 2,382 2,775 10,347 3,673 Other income (expense), net 50 452 8 (1,196)Net loss (62,551) (42,989) (185,701) (319,952)Unrealized gain (loss) on investments 122 (220) 334 (131)Comprehensive loss $(62,429) $(43,209) $(185,367) $(320,083)Net loss per common share: Basic and diluted $(0.71) $(0.50) $(2.14) $(5.06)Weighted-average number of common shares outstanding: Basic and diluted 87,567 85,262 86,798 63,284 ALLAKOS INC. UNAUDITED CONDENSED BALANCE SHEETS (in thousands) December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $66,440 $87,217 Investments 104,354 192,569 Prepaid expenses and other current assets 9,095 29,057 Total current assets 179,889 308,843 Property and equipment, net 33,369 39,144 Operating lease right-of-use assets 24,136 30,225 Other long-term assets 6,216 8,208 Total assets $243,610 $386,420 Liabilities and stockholders’ equity Current liabilities: Accounts payable $1,764 $4,832 Accrued expenses and other current liabilities 34,814 25,206 Total current liabilities 36,578 30,038 Operating lease liabilities, net of current portion 38,215 45,949 Total liabilities 74,793 75,987 Stockholders’ equity: Common stock 88 85 Additional paid-in capital 1,287,156 1,243,408 Accumulated other comprehensive loss 50 (284)Accumulated deficit (1,118,477) (932,776)Total stockholders’ equity 168,817 310,433 Total liabilities and stockholders’ equity $243,610 $386,420

▲3月7-8日 成都生物医药创新者峰会 · 点击立即报名注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。临床试验的失败可能源于多个方面，一项研究表明90%的药物开发临床失败可能有四个原因：缺乏临床疗效（40%-50%）、难以控制的毒性（30%）、类药特性差（10%-15%)，以及缺乏商业需求和战略规划不佳(10%)，包括临床疗效不佳、安全性问题等[1]。据不完全统计，2024年1-2月约有18个失败临床研究，其中12项研究因未达主要研究终点告终。01亚虹医药：APL-1202治疗化疗灌注复发的中高危非肌层浸润性膀胱癌的关键性临床试验2月5日，亚虹医药发布公告宣布其产品APL1202与化疗灌注联合使用治疗化疗灌注复发的中高危非肌层浸润性膀胱癌（NMIBC）的随机、双盲、对照、多中心的关键性临床试验未达到主要研究终点，公司决定终止APL-1202与化疗灌注联合使用在该适应症的进一步开发。APL-1202（商品名唯施可®）是一款口服的可逆性MetAP2抑制剂，具有抗血管生成、抗肿瘤活性及调节肿瘤免疫微环境的作用。此研究是一项随机、双盲、对照、多中心的关键性临床试验，主要研究终点是无事件生存期（EFS，“事件”定义为经病理确认的复发、进展或膀胱癌引起的死亡）。结果显示，尽管在部分患者人群中显示出一定的优效趋势，但是主要疗效指标无事件生存期（EFS）未达到预设的统计假设。除本研究外，公司同时正在开展APL-1202其他2项临床试验。APL-1202单药治疗未经治疗的中危NMIBC的Ⅲ期临床试验（Ascertain）处于临床入组阶段。APL-1202口服联合替雷利珠单抗作为肌层浸润性膀胱癌（MIBC）新辅助治疗的II期临床试验（Anticipate）已经完成所有受试者入组，预计2024年三季度读出Ⅱ期顶线数据。Anticipate研究已完成Ⅱ期临床试验期中分析，结果达到了方案预设要求。02Gilead：magrolimab治疗急性髓性白血病的Ⅲ期ENHANCE-3研究2月7日，Gilead宣布终止CD47单抗magrolimab治疗急性髓性白血病（AML）的3期ENHANCE-3研究，FDA将所有magrolimab治疗骨髓增生异常综合征（MDS）和急性髓性白血病的研究，包括相关的扩大准入项目置于全面临床搁置状态。这些决定是根据独立数据监测委员会的建议做出的，该委员会审查了ENHANCE-3总生存期（OS）中期分析计划的一线数据。在该分析中，magrolimab与阿扎胞苷和venetoclax联用显示出无治疗效果，并观察到死亡风险增加，主要是由感染和呼吸衰竭引起的。另外两项针对高风险MDS（ENHANCE）和TP53突变AML（ENHANCE-2）的临床研究数据的初步分析也表明，在magrolimab治疗组中，患者死亡风险增加，并且药物无治疗效果，基于这些结果吉利德表示将不再进一步开发magrolimab用于治疗血液病。03Synlogic：SYNB1934治疗苯丙酮尿症的Ⅲ期 Synpheny-3研究2月8日，Synlogic公司（纳斯达克股票代码：SYBX）宣布终止Synpheny-3研究，该研究是对labafenogene marselecobac (SYNB1934)作为苯丙酮尿症（PKU）的一种潜在治疗方法正在进行的Ⅲ期临床研究。SYNB1934是利用合成生物学改造的细菌菌株，具有降解苯丙氨酸的能力。终止Synpheny-3试验的决定是基于即将进行的独立数据监测委员会（DMC）评估前的内部审查结果，该结果表明该试验不太可能达到主要终点。该决定并非基于对安全性或耐受性的担忧。Synlogic现在将与相关的Synpheny-3临床试验机构合作，执行终止试验的决定。04阿斯利康：Tozorakimab联合达格列净治疗糖尿病肾病的IIb期临床研究2月8日，阿斯利康在2023年全年业绩报告上公布因疗效不佳，决定终止抗IL-33单抗Tozorakimab联合达格列净治疗糖尿病肾病的IIb期临床研究（NCT04170543）。这项研究旨在评估MEDI3506在标准治疗基础上对糖尿病肾病患者的疗效和安全性。首要目标是评估MEDI3506对糖尿病肾病成年受试者白蛋白尿的影响，次要目标包括评估安全性、PK、治疗期间ADA的发生率。05AN2 Therapeutics：epetraborole治疗难治性肺病的II/III期EBO-301研究2月12日，AN2 Therapeutics宣布自愿暂停无缝II/III期临床试验（EBO-301）中III期研究部分的患者入组，该试验旨在评估口服小分子细菌leucyl-tRNA合成酶抑制剂epetraborole治疗由鸟分枝杆菌复合体（MAC）引起的难治性肺病的疗效与安全性。这项双盲、安慰剂对照的临床试验共分为两个队列，对比epetraborole+优化背景方案（OBR）与安慰剂+OBR的疗效。II期研究部分已于2023年9月完成了80例患者的入组，III期研究部分迄今为止招募了近100例患者，已入组患者将被允许继续参与研究。在对正在进行的第二阶段研究进行盲法汇总分析后，发现疗效可能低于预期，因此决定自愿暂停试验。这一决定并非出于安全考虑，2期试验的目的是为3期试验提供依据。公司预计将于2024年夏季公布2期试验的初步数据。06大冢制药：AVP-786治疗阿尔茨海默病痴呆相关激越的III期临床研究2月12日，大冢制药公布了AVP-786（氘代右美沙芬+奎尼丁）治疗阿尔茨海默病痴呆相关激越的III期临床试验（NCT03393520）未达主要疗效终点。AVP-786是氘代的氢溴酸右美沙芬和CYP2D6抑制剂硫酸奎尼丁的复方制剂。据观察，氘化可显著降低对细胞色素P450（CYP2D6）酶代谢的敏感性，从而提高生物利用度。在主要疗效终点（Cohen-Mansfield激越量表（CMAI）总分从基线到第12周的平均变化）上，AVP-786和安慰剂之间没有达到统计学意义上的显著差异。07Roivant Sciences：RVT-2001用于治疗骨髓增生异常综合征的I/II期试验2月13日，Roivant Sciences在财报中披露终止开发SF3B1调节剂RVT-2001用于治疗骨髓增生异常综合征的临床I/II期试验，原因是期中分析结果后有效性不及预期。2022年，Roivant与卫材（Eisai）达成了一项许可协议，获得在研药物RVT-2001的全球独家权利，RVT-2001是一款潜在的first-in-class口服小分子剪接因子SF3B1调节剂，RVT-2001已经在19例低风险、输血依赖性MDS患者中，让超过30%的患者不依赖血红细胞输注。08Denali/赛诺菲：DNL788治疗肌萎缩侧索硬化症的II期HIMALAYA研究2月16日，Denali Therapeutics在SEC文件中透露，DNL788（SAR443820）治疗肌萎缩侧索硬化症（ALS）的II期HIMALAYA研究未能达到显著改善修订版ALS功能评定量表（ALSFRS-R）评分的主要终点。受此消息影响，Denali的股价下跌了近8%。2018年10月，赛诺菲和Denali公司就RIPK1抑制剂的全球开发和商业化展开广泛合作。赛诺菲将领导SAR443820/DNL788治疗ALS和MS的1期临床和2期临床开发，并与Denali公司一起进行该药治疗ALS、MS和阿尔茨海默病的3期临床试验。SAR443820/DNL788是由赛诺菲和Denali共同开发的一款有效的、选择性的、具有脑渗透性的RIPK1抑制剂。赛诺菲将继续在多发性硬化症患者中开展SAR443820/DNL788的K2 2期研究；1月8日，Denali在新闻稿中透露，赛诺菲已完成SAR443820/DNL788治疗多发性硬化症（MS）的2期试验，共招募174名参与者。09Theravance Biopharma：Yupelri治疗COPD的IV期PIFR-2研究2024年1月5日，Theravance Biopharma宣布Yupelri（revfenacin）吸入溶液用于慢性阻塞性肺病（COPD）维持治疗的IV期PIFR-2研究未达主要终点。Yupelri 是美国批准用于慢阻肺维持治疗的唯一每日一次的雾化长效毒蕈碱拮抗剂（LAMA）。这项PIFR-2研究旨在评估，Yupelri较噻托溴铵（Spiriva，粉雾剂）在严重至极为严重COPD患者的肺功能改善情况。研究结果显示，第85天时第一秒用力呼气谷值较基线变化的主要终点指标方面，与对照组相比，Yupelri并未有统计学显著差异。Yupelri的安全性与耐受性与既往研究一致。本次研究的失败也导致Theravance股价下跌10%。10Allakos：lirentelimab治疗特应性皮炎的II期ATLAS研究和治疗慢性自发性荨麻疹的IIb期MAVERICK研究1月16日，Allakos宣布lirentelimab在治疗特应性皮炎患者的2期临床试验（ATLAS）和治疗慢性自发性荨麻疹患者的2b期临床试验（MAVERICK）中均未达主要终点。Lirentelimab治疗特应性皮炎患者的2b期临床试验（ATLAS）研究结果显示，在主要终点治疗后达到EASI-75上，接受Lirentelimab治疗的患者达到EASI-75的患者比例为23%，而接受安慰剂治疗的患者中这一比例为18%，不具有统计学意义。在MAVERICK试验中，主要终点UAS7减少比例上，Lirentelimab治疗患者的UAS7减少了27%，而安慰剂治疗患者中这一比例为26%，也不具有统计学意义。11Gilead：Trodelvy治疗经治转移性或晚期非小细胞肺癌的III期EVOKE-01研究2024年1月22日，Gilead公布Trop2 ADC新药Trodelvy治疗非小细胞肺癌的三期临床EVOKE-01研究没有达到OS主要终点。EVOKE-01正在评估Trop2 ADC药物Trodelvy®（sacituzumab-govitecan-hziy；SG）与多西他赛在铂类化疗和检查点抑制剂治疗期间或之后进展的转移性或晚期NSCLC患者中的疗效。Trodelvy是一款Trop-2 ADC单抗药物。Trop-2是一种跨膜糖蛋白，它的高表达与很多肿瘤的发生以及预后较差相关，是一个非常热门的ADC研究靶点，热度仅次于HER2。目前全球只有吉利德的Trop-2 ADC药物Trodelvy获批上市，用于治疗既往接受过至少2种疗法的转移性三阴乳腺癌（mTNBC）成人患者和局部晚期或转移性尿路上皮癌（UC）患者。Trodelvy的试败导致吉利德股价在达到11个月高点后，周一暴跌约10%。12BMS：Opdivo治疗肌萎缩侧索硬化症的III期CheckMate-914研究1月29日，百时美施贵宝（BMS）宣布其PD-1抑制剂Opdivo在III期CheckMate-914研究的B部分中失败，对于术后存在高复发风险的局部肾细胞癌患者未带来显著的无病生存益处。CheckMate-914是一项随机、双盲、两部分的试验。在B部分中，该研究将Opdivo单药疗法与安慰剂对比。此试验评估其作为肾细胞癌（RCC）患者的辅助治疗。这些患者已经完全或部分切除肾脏，并且处于中度或高度复发风险。在中位随访27个月后，Opdivo未能在病情无进展生存期（DFS）方面取得显著改善，根据盲目独立中央审查（BICR）的评估，与安慰剂相比，Opdivo的效果呈现出0.87的风险比，p值为0.3952。在Opdivo组的12个月DFS概率为83.3%，而安慰剂组为78.2%。在18个月时，这些估计仅略有变化，分别为78.4%和75.4%。在分析时，两个治疗组的DFS中位数均未达到。13来凯医药：afuresertib联合紫杉醇治疗耐药卵巢癌的II期临床研究1月29号，来凯医药公布afuresertib联合紫杉醇治疗耐药卵巢癌（PROC）（PROFECTA-II）的顶线数据。PROFECTA-II研究（NCT04374630）是一项随机、开发标签、有效对照的2期临床试验，评估afuresertib合紫杉醇治疗与单独紫杉醇对照铂耐药卵巢癌（PROC）女性患者的疗效和安全性。研究在美国和中国随机入组了150名患者到试验组和对照组。主要终点为研究者评估的无进展生存期，次要终包括总生存期、客观缓解率和持续缓解时间。试验结果表明，afuresertib联合紫杉醇治疗可以降低疾病展或死亡的风险（无进展生存期，PFS )，HR为0.744（95%CI:0.502-1.102），但试验结果不具有统计学意义。总结据公开资料显示，2024年伊始已有18款药物在临床中折戟，终止临床二期和临床三期试验的原因中疗效仍然是最关键的原因，在肿瘤和CNS疾病中这一比例更大，这也反映出这些疾病的复杂性和异质性，仍需更多耐力去克服。虽然II期试验中因安全性原因导致失败的比例有所增加，但在III期中，这一原因的占比正在减少，这说明研发越来越在安全性下功夫，可以在研发早期就筛除安全性差的产品。在研发新药的路上只有战胜挫折，拥有接受困难的勇气，才有机会让罹受疾病困扰的人民重获新生。参考文献：[1]Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it?. Acta Pharm Sin B. 2022;12(7):3049-3062.[2]各公司官网版权声明：本文转自生物药大时代，如不希望被转载的媒体或个人可与我们联系，我们将立即删除 活动推荐  3月 • NDC x 2024新药创新者峰会  关键词：  ADC，改良型新药，小分子新药，GLP-1药物（点击下方图片查看详情）▼【关于药融圈】药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。