Pacira Biosciences, Inc.

Boston biotech Axonis Therapeutics has raised a $115 million Series A to test whether its oral drug AXN-027 can help patients with focal epilepsy and diabetic neuropathic pain. The financing, disclosed Wednesday morning, will get the biotech into the clinic around the end of this year, or about the same time Ovid Therapeutics expects to begin human trials with a similar approach by way of an AstraZeneca platform it licensed. Both companies are looking at KCC2, a CNS chloride transporter that is key to electrical signaling in the brain. KCC2 allows for neuronal GABA signaling. The GABA pathway has been targeted by multiple drugmakers , including Sage’s postpartum depression medicine Zurzuvae , but biotechs have yet to enter the clinic with a focus on KCC2, CEO Joanna Stanicka told Endpoints News . “Often GABA treatments can induce global inhibition, which leads to this cognitive impairment and sedation often reported by patients,” Stanicka said, adding that focused inhibition should avoid those side effects. The 13-employee biotech also said Wednesday that it added Donald Manning as chief medical officer and Jeff Imbaro as operating chief. Manning previously held the same post at Travecta, Pacira BioSciences and Adynxx. Imbaro was in the same role at stroke-focused Elevian, and before that he was a founding member of Vertex-acquired Semma Therapeutics. Axonis was founded by spinal cord injury patient advocate and board observer Bob Yant about 15 years ago, but it didn’t become “operational” until 2019, Stanicka said. Prior to the Series A, Axonis had raised about $34 million in seed funding and about $9 million in government and foundation money, Stanicka said. Its investors include Cormorant Asset Management, venBio, Sofinnova Investments, Merck’s corporate venture arm and others. The startup anticipates the Series A will fund AXN-027 through Phase 2 proof-of-concept studies, she said.

奔赴全球市场，已成为恒瑞医药的发展主线。 正如恒瑞医药副总经理张连山此前在接受媒体采访时表示，“海外战略上我们有所调整，现在每个产品都愿意寻求合作。” 从去年达成5个跨境license-out交易，到今年成功运用NewCo模式将GLP-1产品组合以总价超60亿美元授权出海，恒瑞的BD出海策略愈加成熟。 近期，更是有媒体报道称，恒瑞聘请了强生BD老将Jens Bitsch-Norhave担任“全球发展事务负责人”，也就是海外BD高管。 这表明，恒瑞又在全球市场布下了一颗“重要棋子”，驶向全球市场的决心可见一斑。 01 全球化野望 每一家药企都想奔赴全球化的“星辰大海”，恒瑞医药亦不例外。 然而，需要明确的是，开拓全球市场的方式多样，并不仅限于BD（业务发展）合作。其中，境外融资也常常成为企业打入国际市场的重要桥梁。 比如近日就有市场传闻称，“恒瑞正在考虑明年赴港上市，拟募资至少20亿美元”。 对此，恒瑞发布公告作出回应，“近年来，在科技创新和国际化发展战略驱动下，公司稳步推进国际化进程。为进一步深化公司战略发展目标，公司近期对境外资本市场融资等事项开展了研究咨询等前期工作。截至目前，公司就相关事项尚未确定具体方案。” 尽管恒瑞对于是否赴港上市没有给出正面回应，但其透露出的研究境外资本市场融资等事项的信号却十分明确。这也从侧面体现出恒瑞渴望驶向更广阔海外市场的野心。 图片来源：恒瑞医药公告 从频繁达成出海交易，到聘请强生老将担任海外BD高管，再到研究境外资本市场融资，恒瑞为何加码海外市场？这一点可从百济神州的国际化成就得到直观反映。 今年上半年，“创新药一哥”百济神州实现总营收达119.96亿元，而其之所以能实现半年收入即突破百亿大关，主要得益于泽布替尼和替雷利珠单抗。 这两款拳头产品能保持快速增长态势，很大程度要归功于海外市场的贡献。 泽布替尼能成为国产创新药首个“十亿美元分子”，得益于已在美国、中国、欧盟等超70个市场获批多项适应症，其中美国市场贡献了大部分收入，同比增长134.4%至59.03亿元，欧洲市场也以231.6%的同比增速首次突破10亿元大关。 对比来看，今年上半年恒瑞医药的创新药收入为66.12亿元（含税，不含对外许可收入），由16款创新药合计贡献，仍不及泽布替尼一款产品（全球销售额达80.18亿元）。 另外，替雷利珠单抗半年销售额超20亿元，也少不了在美国、欧盟、英国和澳大利亚获批上市的助力。尤为值得一提的是，替雷利珠单抗在美国市场的定价是国内的20多倍。 相较之下，恒瑞的“双艾组合”曾闯关FDA失利，近期才重新提交一线治疗肝细胞癌的上市申请，PDUFA目标日期为2025年3月23日。 正如张连山在接受媒体采访时表示，“过去卡瑞利珠单抗联合阿帕替尼组合的出海方式，放到现在，我们不会这么做，因为成本太大。我们改变策略，任何一个产品，在任何临床阶段，都会寻求跟海外合作开发。” 可见，恒瑞不仅要剑指全球市场，还将以多样化的策略加速产品国际化进程。 02 全球化之路“遍地开花” 恒瑞医药全力以赴走向全球市场，也与其尝到了创新药收入及BD贡献业绩的甜头有关。 尽管目前创新药的销售体量不及百济神州，但恒瑞也在今年上半年交出了靓丽的业绩：实现总营收136.01亿元，同比增长21.78%；归母净利润34.32亿元，同比大增48.67%。 更重要的是，恒瑞的创新药收入达66.12亿元（含税，不含对外许可收入），如果加上德国Merck（默克）公司支付的1.6亿欧元对外许可首付款，创新药收入总和占总营收比重已经过半。 这一份超乎预期的成绩单，让市场不禁感叹：“医药一哥”回来了。 此外，恒瑞还在今年5月将GLP-1产品组合授权给美国Hercules公司，不仅达成总额超60亿美元的合作（其中首付款和近期里程碑付款总计1.1亿美元），还获得了Hercules公司19.9%的股权。 按照以往6个月后确认收入的惯例，恒瑞大概率会在第四季度将GLP-1的首付款确认为收入，并计入当期利润。但这还仅仅是冰山一角。 恒瑞这两年一直在积极向海外药企授出管线资产，2023年达成了5个跨境license-out交易，其中就包括将PARP1抑制剂HRS-1167和Claudin18.2 ADC药物SHR-A1904以总价14亿欧元授权给Merck公司。 这意味着，恒瑞有望迎来源源不断的合作收入，创新药板块将演变为“里程碑+商业化”双轮收入结构。 今年下半年，恒瑞也在海外市场收获了一些成效： 7月，布比卡因脂质体注射液的ANDA（简略新药申请，即美国仿制药申请）获FDA批准，成为该品种在全球范围内获批上市的首仿药。 据介绍，布比卡因脂质体注射液最早由美国Pacira公司研制，2011年在美国获批上市，目前仅在美国和欧洲销售，国内尚未进口。因其技术壁垒高，上市十余年无仿制产品成功上市。2023年，布比卡因脂质体相关剂型全球销售额约为5.38亿美元。 10月，注射用紫杉醇（白蛋白结合型）的ANDA获FDA批准，成为美国FDA批准上市的该品种首仿药。 需要注意的是，注射用紫杉醇（白蛋白结合型）由美国阿博利斯生命科学公司开发，最早于2005年获得FDA批准上市，商品名为Abraxane，现已在美国、欧盟、日本等多个国家和地区上市。经查询，注射用紫杉醇（白蛋白结合型）2023年全球销售额合计约25.97亿美元。 恒瑞医药的雄心远不止于此。首仿药的获批只是其国际化战略的一个缩影，还有一系列正在海外进行临床试验的创新药，未来也有望在国际市场上开辟新的增长点。 03 “双艾”组合再冲FDA，抗肿瘤领域成“重头戏” 正在海外推进临床试验的创新药，将是恒瑞医药未来竞争的“制胜法宝”。 截至今年7月31日，恒瑞共有17款创新药在海外进入临床研究阶段，其中抗肿瘤领域11款、自身免疫领域3款，血液/抗肿瘤、呼吸系统和其他领域各1款。 从临床进度看，进展最快的是“双艾组合”（卡瑞利珠单抗联合阿帕替尼），在近期重新向FDA提交了一线治疗肝细胞癌的上市申请。根据处方药用户付费法案（PDUFA）， FDA对卡瑞利珠单抗的目标审评日期为2025年3月23日。 图片来源：恒瑞医药2024年中报 另外，恒瑞在抗肿瘤领域的海外创新药中，ADC药物的比例高达一半，包括SHR-A1811（HER2 ADC）、SHR-A1904（Claudin 18.2 ADC）、SHR-A1912（CD79b ADC）、SHR-A1921（TROP2 ADC）、SHR-A2009（HER3 ADC）、SHR-A2102（Nectin-4 ADC），其中已有4款ADC药物获得FDA授予快速通道资格认定。 今年9月，恒瑞在ESMO年会上公布了SHR-A1904治疗胃或胃食管交界处癌（GC/GEJC）的I期研究结果：在基线和≥1次基线后评估的患者中，6.0 mg/kg剂量组中，客观缓解率（ORR）达55.6%、疾病控制率（DCR）达88.9%，具有可管理的安全性和良好的抗肿瘤活性，临床潜力可期。 恒瑞还在2024 ESMO年会上公布了SHR-A2102治疗晚期实体瘤患者的I期研究结果：在经过多线治疗的非小细胞肺癌（NSCLC）患者中，ORR、DCR分别高达31.3%、87.5%。目前，全球仅有一款Nectin-4 ADC药物获批上市，而且市场竞争格局相对缓和。 另外，TROP2 ADC药物SHR-A1921也展示出鼓舞人心的临床研究数据：单药治疗复发性铂耐药卵巢癌的ORR大于40%，且缓解具有可持续性；中位PFS达到7个月左右；推荐剂量下安全性可控、耐受性良好，有望改变铂耐药复发上皮性卵巢癌的治疗现状。 值得一提的是，SHR-A1921也在开展用于预后差且治疗方案有限的广泛期小细胞肺癌（ES-SCLC）患者的临床试验，Ⅰ期试验显示出了令人鼓舞的疗效：截至2024年2月19日，共有17名患者入组，在15例可评估肿瘤反应的患者中，ORR为33.3%，DCR为66.7%，中位DoR为4.4个月。在所有患者中，中位PFS为3.8个月，中位OS未达到。 可见，“医药一哥”恒瑞医药在海外创新药领域的持续投入和精心耕耘，如今正在逐渐结出硕果，其未来发展值得期待。 参考资料 1.各家公司的财报、公告、官微 2.《恒瑞医药海外上市没那么可怕》，见智研究Pro 3.交银国际证券研报

-- New J-code issued by the Centers for Medicare and Medicaid Services expected to standardize and streamline billing and reimbursement -- TAMPA, Fla., Oct. 03, 2024 (GLOBE NEWSWIRE) -- Pacira BioSciences, Inc. (NASDAQ: PCRX), the industry leader in the delivery of innovative, non-opioid pain therapies, today announced that the Centers for Medicare and Medicaid Services (CMS) has established a permanent product-specific Healthcare Common Procedure Coding System (HCPCS) J-code for EXPAREL® (bupivacaine liposome injectable suspension). The new J-code for EXPAREL, J0666, becomes effective January 1, 2025, and will supersede the current C-code (C9290), which has been in place since 2019. In addition to the separate CMS reimbursement EXPAREL will receive in outpatient settings with the implementation of NOPAIN in January 2025, this new J-code will also provide reimbursement when EXPAREL is used in the office setting and for office-based surgeries. J-codes are reimbursement codes used by commercial insurance plans, Medicare, Medicare Advantage, and other government payers for Medicare Part B drugs like EXPAREL. Claims submission and payment are standardized with a J-code, facilitating and streamlining billing and reimbursement. In addition, some commercial insurers require a J-code for payment. “We are pleased that EXPAREL will have its own product-specific J-code beginning on January 1, 2025,” said Frank D. Lee, chief executive officer of Pacira. “In addition to streamlining the reimbursement billing and coding process at large, a J-code is also more likely to be recognized and covered by commercial payers—a growing portion of the EXPAREL patient population. This, combined with the impending reimbursement from NOPAIN, is particularly important toward increasing clinician access to EXPAREL across sites of care and payer types, offering them the enhanced ability to offer a best-in-class option for achieving long-lasting non-opioid pain control with an increased ability to transition procedures to outpatient settings.” EXPAREL is indicated to produce postsurgical local analgesia via infiltration in patients aged 6 years and older and regional analgesia in adults via an interscalene brachial plexus nerve block, sciatic nerve block in the popliteal fossa, and an adductor canal block. Safety and efficacy have not been established in other nerve blocks. It has been used in over 15 million patients across the United States to date. About Pacira BioSciencesPacira BioSciences delivers innovative, non-opioid pain therapies to transform the lives of patients. Pacira has three commercial-stage non-opioid treatments: EXPAREL® (bupivacaine liposome injectable suspension), a long-acting local analgesic currently approved for infiltration, fascial plane block, and as an interscalene brachial plexus nerve block for postsurgical pain management; ZILRETTA® (triamcinolone acetonide extended-release injectable suspension), an extended-release, intra-articular injection indicated for the management of osteoarthritis knee pain; and ioveraº®, a novel, handheld device for delivering immediate, long-acting, drug-free pain control using precise, controlled doses of cold temperature to a targeted nerve. The company is also advancing the development of PCRX-201, a novel locally administered gene therapy with the potential to treat large prevalent diseases like osteoarthritis. To learn more about Pacira, visit www.pacira.com. About EXPAREL®EXPAREL (bupivacaine liposome injectable suspension) is indicated to produce postsurgical local analgesia via infiltration in patients aged 6 years and older, and postsurgical regional analgesia via an interscalene brachial plexus block in adults, a sciatic nerve block in the popliteal fossa in adults, and an adductor canal block in adults. The safety and effectiveness of EXPAREL have not been established to produce postsurgical regional analgesia via other nerve blocks besides an interscalene brachial plexus nerve block, a sciatic nerve block in the popliteal fossa, or an adductor canal block. The product combines bupivacaine with multivesicular liposomes, a proven product delivery technology that delivers medication over a desired time period. EXPAREL represents the first and only multivesicular liposome local anesthetic that can be utilized in the peri- or postsurgical setting. By utilizing the multivesicular liposome platform, a single dose of EXPAREL delivers bupivacaine over time, providing significant reductions in cumulative pain scores with up to a 78 percent decrease in opioid consumption; the clinical benefit of the opioid reduction was not demonstrated. Additional information is available at www.EXPAREL.com. Forward-Looking StatementsAny statements in this press release about Pacira’s future expectations, plans, trends, outlook, projections and prospects, and other statements containing the words “anticipate,” “believe,” “can,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “project,” “should,” “will,” “would,” and similar expressions, constitute forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and the Private Securities Litigation Reform Act of 1995, including, without limitation, statements related to our intellectual property, our growth and future operating results and trends, our strategy, plans, objectives, expectations (financial or otherwise) and intentions, future financial results and growth potential, including our plans with respect to the repayment of our indebtedness, anticipated product portfolio, development programs, patent terms, development of products, strategic alliances, plans with respect to the Non-Opioids Prevent Addiction in the Nation (“NOPAIN”) Act and other statements that are not historical facts. For this purpose, any statement that is not a statement of historical fact should be considered a forward-looking statement. We cannot assure you that our estimates, assumptions and expectations will prove to have been correct. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to, among others: the integration of our new chief executive officer; risks associated with acquisitions, such as the risk that the acquired businesses will not be integrated successfully, that such integration may be more difficult, time-consuming or costly than expected or that the expected benefits of the transaction will not occur; our manufacturing and supply chain, global and U.S. economic conditions (including inflation and rising interest rates), and our business, including our revenues, financial condition, cash flow and results of operations; the success of our sales and manufacturing efforts in support of the commercialization of EXPAREL, ZILRETTA and iovera°; the rate and degree of market acceptance of EXPAREL, ZILRETTA and iovera°; the size and growth of the potential markets for EXPAREL, ZILRETTA and iovera° and our ability to serve those markets; our plans to expand the use of EXPAREL, ZILRETTA and iovera° to additional indications and opportunities, and the timing and success of any related clinical trials for EXPAREL, ZILRETTA and iovera°; the commercial success of EXPAREL, ZILRETTA and iovera°; the related timing and success of U.S. Food and Drug Administration supplemental New Drug Applications and premarket notification 510(k)s; the related timing and success of European Medicines Agency Marketing Authorization Applications; our plans to evaluate, develop and pursue additional product candidates utilizing our proprietary multivesicular liposome (“pMVL”) drug delivery technology; the approval of the commercialization of our products in other jurisdictions; clinical trials in support of an existing or potential pMVL-based product; our commercialization and marketing capabilities; our ability to successfully complete capital projects; the outcome of any litigation; the ability to successfully integrate any future acquisitions into our existing business; the recoverability of our deferred tax assets; assumptions associated with contingent consideration payments; the anticipated funding or benefits of our share repurchase program; and factors discussed in the “Risk Factors” of our most recent Annual Report on Form 10-K and in other filings that we periodically make with the Securities and Exchange Commission (the “SEC”). In addition, the forward-looking statements included in this press release represent our views as of the date of this press release. Important factors could cause actual results to differ materially from those indicated or implied by forward-looking statements, and as such we anticipate that subsequent events and developments will cause our views to change. Except as required by applicable law, we undertake no intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, and readers should not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this press release.