Ficlatuzumab

2024年7月18日，LG化学公司旗下的AVEO Oncology宣布，在接受免疫检查点抑制剂 (ICI) 治疗后肿瘤出现进展的晚期转移性肾细胞癌 (RCC) 患者中开展的TiNivo-2 3期临床试验，将Opdivo（nivolumab）与低剂量 (0.89 mg) FOTIVDA (tivozanib) 联合治疗时未达到增加无进展生存期 (PFS) 的主要终点。 TiNivo-2临床试验旨在评估在ICI联合治疗后二线治疗或先前ICI治疗后三线治疗中，将PD-1检查点抑制剂nivolumab添加到低剂量FOTIVDA中与标准剂量FOTIVDA相比的益处。TiNivo-2临床试验招募了北美、拉丁美洲和欧洲临床中心的患者。接受免疫治疗后病情进展的RCC患者被随机分配接受tivozanib单药治疗或与 nivolumab 联合治疗。试验的主要结果是无进展生存期；次要终点包括总生存期、总缓解率、缓解持续时间和安全性。 尽管该组合药物的3期临床试验在PFS方面失败，但AVEO对于对照组的结果抱有积极态度。对照组使用标准剂量 (1.34 mg) 的FOTIVDA作为单药治疗，在ICI联合治疗后的二线治疗中显示出中位PFS具有临床意义的结果。这些结果以TIVO-3临床试验（FOTIVDA 的关键性3期研究）的先前ICI数据集为基础，进一步支持批准使用FOTIVDA作为在接受两次或两次以上全身治疗后复发或难治性晚期RCC的安全有效治疗选择。 AVEO Oncology首席执行官兼总裁 Michael P. Bailey 表示：“在ICI联合治疗后二线治疗中，FOTIVDA对照组的PFS和安全性进一步证明了高选择性抗VEGFR TKI疗法的重要性，该疗法是一种有效且耐受性良好的治疗选择，适用于接受过ICI联合治疗的复发或难治性RCC患者。虽然在低剂量 FOTIVDA中添加ICI并未改善先前ICI后的PFS结果，但我们认为对照组数据对治疗一线ICI联合治疗后复发或难治性晚期RCC的肿瘤学界来说是一项重要的、基于证据的、具有临床意义的贡献。” 跌宕起伏的FOTIVDA FOTIVDA是一种口服的下一代血管内皮生长因子受体 (VEGFR) 酪氨酸激酶抑制剂 (TKI)。它是一种强效的 VEGFR 1、2 和 3 选择性抑制剂，具有较长的半衰期。 Fotivda经历了漫长的上市之路，但最终获得了 FDA 的批准。2021年3月AVEO的新药FOTIVDA获得FDA的批准，用于治疗成年患者在两种或两种以上全身性治疗后复发或难治性RCC。而且，在此之前FOTIVDA于2017年8月在欧盟、挪威、新西兰、冰岛等已获得批准，用于晚期RCC成年患者。 AVEO早在2013年就向FDA提交了VEGF受体抑制剂tivozanib用于肾癌的申请。但是，FDA专家小组对AVEO的试验产生了质疑，原因是患者服用索拉非尼的生存期比使用tivozanib的生存期更长，并最终导致AVEO的申请并没有被通过。这个结果甚至引起AVEO的股价暴跌，还失去了Astellas这个重要合作伙伴。 但在被FDA拒绝之后，AVEO并没有放弃对tivozanib的研究和试验。AVEO又开展了TIVO-3的开放标签III期研究，比较tivozanib和索拉非尼用于RCC的疗效，并宣称研究达到了主要终点，证明无进展生存时间（PFS）有显著改善。但遗憾的是，2019年11月FDA对AVEO提交的数据进行梳理之后，再次拒绝了AVEO 关于VEGF 受体抑制剂tivozanib的申请。 直到2021年2月22日，AVEO宣布FOTIVDA最终获得美国FDA的批准。 2022 年 10 月，AVEO被LG Chem收购，LG Chem以5.66亿美元溢价 43%的价格收购了AVEO，从而获得了Fotivda和Aveo的其他抗癌药物组合。 除了FOTIVDA，AVEO Oncology多种单克隆抗体正处于临床试验阶段。 Ficlatuzumab（研究代码为 AV-299）：是一种强效的人源化 IgG1 单克隆抗体，靶向肝细胞生长因子（HGF）。2022 年，美国FDA将ficlatuzumab和 Erbitux（西妥昔单抗）用于治疗复发/复发性 (R/R) 头颈部鳞状细胞癌 (HNSCC) 的调查指定为快速通道开发计划。 AV-380：是AVEO的首创、强效、人源化抑制性IgG1抗体，靶向生长分化因子15 (GDF15)。GDF15是一种促炎细胞因子，其循环水平升高与癌症恶病质患者和几种癌症恶病质动物模型中的恶病质有关。目前正在进行针对癌症患者的 1b 期临床试验。 AV-203：是一种临床阶段的 ErbB3 (HER3) 抑制抗体候选药物，旨在抑制配体依赖性和配体非依赖性 ErbB3 信号传导。ErbB3 是一种通常在多种人类癌症中表达的受体，AV-203 已在多种不同的肿瘤模型中表现出临床前活性，包括乳腺癌、头颈癌、肺癌、卵巢癌和胰腺癌。一项AV-203治疗晚期实体瘤患者的1期开放标签剂量递增研究表明，AV-203总体上安全的且耐受性良好，其早期活性信号与临床前数据一致，表明唯一已知的ErbB3 配体 heregulin 或 neuregulin 有可能作为预测 AV-203 抗肿瘤活性的生物标志物。 资料来源： 1.公司官网 2.LG Chem picks up Aveo and its kidney cancer drug Fotivda for $566M.By Kevin Dunleavy  Oct 18, 2022 3.Aveo spins a silver lining in failed trial of kidney cancer drug Fotivda.By Kevin Dunleavy  Jul 18, 2024 4.FDA tells Aveo no, again, for tivozanib as biotech tries to find yet another path forward.By Ben Adams  Nov 4, 2019 5.Aveo Oncology’s Fotivda combo fails in Phase 3 kidney cancer test.Ayisha Sharma 识别微信二维码，添加生物制品圈小编，符合条件者即可加入 生物制品微信群！ 请注明：姓名+研究方向！ 版 权 声 明 本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

Earned $9 million milestone upon U.S. Food and Drug Administration’s approval of Day One’s OJEMDA™ (tovorafenib); XOMA is entitled to receive a mid-single digit royalty on OJEMDA™ sales Acquired Kinnate Pharmaceuticals, adding at least $9.5 million in non-dilutive capital to XOMA’s balance sheet Expanded the commercial royalty and milestone portfolio with the acquisitions of economic interests in DSUVIA® (sufentanil sublingual tablet) and XACIATO™ (clindamycin phosphate) vaginal gel 2%, as well as two Phase 3 assets Launched XOMA’s first stock repurchase program for up to $50 million EMERYVILLE, Calif., May 09, 2024 (GLOBE NEWSWIRE) -- XOMA Corporation (NASDAQ: XOMA), the biotech royalty aggregator, reported its first quarter 2024 financial results and highlighted recent activities. “We continue to build the foundation for accelerating value creation with a disciplined approach to capital deployment,” stated Owen Hughes, Chief Executive Officer of XOMA. “In recent months, we’ve completed the acquisition of Kinnate, acquired economic interests in two commercial assets, as well as in two first-in-class Phase 3 assets, and initiated our first share buyback program on the heels of securing the VABYSMO® royalty-backed loan with Blue Owl. Lastly, and most importantly, the FDA approved OJEMBA™ (tovorafenib), Day One Biopharmaceuticals’ type II RAF inhibitor for patients with relapsed or refractory pLGG harboring a BRAF fusion or rearrangement or BRAF V600 mutation, ushering in an important new treatment for children living with relapsed or refractory pLGG.” Key First Quarter Events PartnerEventTalpheraXOMA added another commercial asset to its royalty portfolio with an economic interest in DSUVIA®, which is marketed by Alora Pharmaceuticals. XOMA receives 100 percent of the DSUVIA® economics until a threshold is achieved; thereafter, XOMA retains the 15 percent royalty associated with DSUVIA® commercial sales. The 75 percent royalties from Department of Defense purchases and remaining milestone payments will be shared equally between XOMA and Talphera.Kinnate PharmaceuticalsXOMA initiated the acquisition of Kinnate Pharmaceuticals for $2.5879 in cash per share, plus a non-tradeable contingent value right (CVR) representing the right to receive 85 percent of the net proceeds from the out license or sale of Kinnate assets effected on or before April 2, 2025, and 100% of the net proceeds received from Pierre-Fabre.Zevra TherapeuticsU.S. Food and Drug Administration (FDA) accepted the arimoclomol NDA resubmission for review and set a Prescription Drug User Fee Act (PDUFA) action date of September 21, 2024. XOMA paid a $1 million milestone to LadRx based upon the achievement of this milestone.MedexusFDA approved the pediatric label expansion application for IXINITY® [coagulation factor IX (recombinant)].TakedaReported positive topline results from Phase 2 study evaluating mezagitamab (TAK-079), a potential best-in-class anti-CD38 monoclonal antibody for primary immune thrombocytopenia (ITP).iLG Chem (AVEO Oncology)Dosed the first patient in the ficlatuzumab Phase 3 study, resulting in a $1 million milestone payment to XOMA.CompugenReceived a $1 million milestone payment from Compugen. Subsequent Events PartnerEventDay One BiopharmaceuticalsFDA approved Day One’s OJEMDA™ (tovorafenib) for use in pediatric patients with pediatric low-grade glioma (pLGG). XOMA earned a $9 million milestone upon the approval and is entitled to receive mid-single digit royalties from OJEMDA sales.Daré BioscienceXOMA added economic interests to three best- or first-in-category assets to its portfolio. XACIATO™ vaginal gel 2% is commercially available and marketed by Organon. Bayer holds the U.S. rights to commercialize Ovaprene®, a hormone-free monthly intravaginal contraceptive, currently in Phase 3 clinical trials. XOMA also acquired a synthetic royalty in Sildenafil Cream, 3.6%, a Phase 3-ready asset for female sexual arousal disorder.RezoluteDosed first patient in its Phase 3 trial of RZ358; XOMA earned a $5.0 million milestone associated with the event. Anticipated 2024 Events of Note PartnerEventZevra TherapeuticsSeptember 21, 2024 – FDA PDUFA action date for arimoclomol NDATakedaIn its press release dated March 13, 2024, Takeda announced plans to initiate a global Phase 3 trial of mezagitamab in ITP in fiscal year 2024.ii First Quarter 2024 Financial Results XOMA recorded total revenues of $1.5 million for the first quarter of 2024, which included a $1.0 million milestone payment received from AVEO Oncology, as compared with $0.4 million in the first quarter of 2023. Research and development (R&D) expenses were $33,000 and $54,000, respectively, for the first quarters of 2024 and 2023. Upon closing the Kinnate merger in the second quarter of 2024, XOMA assumed operations of Kinnate’s pipeline, as well as ongoing Phase 1 study, and will incur increased R&D costs until winddown activities are complete. General and administrative (“G&A”) expenses were $8.5 million for the first quarter of 2024, compared to $6.2 million for the first quarter of 2023. The increase of $2.3 million was primarily due to a $1.3 million increase in stock-based compensation and a $0.7 million increase in consulting and legal expenses. The increase in stock-based compensation expenses was largely due to the appointment of Mr. Hughes as our full-time Chief Executive Officer in January 2024. In the first quarter of 2024, G&A expenses included $2.9 million in non-cash stock-based compensation expense, compared with $1.6 million in the first quarter of 2023. The increase in stock-based compensation expenses was largely due to the PSU grant associated with the appointment of Mr. Hughes as our full-time Chief Executive Officer in January 2024 combined with PSUs granted in May 2023. Interest expense in the first quarter of 2024 was $3.6 million, representing interest related to the Blue Owl Loan established in December 2023. The Company reported total other income, net, of $2.0 million in the first quarter of 2024, as compared to total other income, net, of $0.4 million in the corresponding period of 2023. The $1.6 million increase reflects a $1.3 million increase in investment income due to higher cash balances and higher market interest rates on our investments, as well as the change in the market price of Rezolute’s common stock. Net loss for the first quarter of 2024 was $8.6 million, compared to a net loss of $9.8 million for the first quarter of 2023. On March 31, 2024, XOMA had cash and cash equivalents of $142.4 million (including $6.2 million in restricted cash). On December 31, 2023, XOMA had cash and cash equivalents of $159.6 million (including $6.3 million in restricted cash). During the first quarter of 2024, XOMA received $9.8 million in cash from royalty and milestone payments and deployed $8 million to acquire new royalty and milestone economic interests. Net cash used in operating activities during the quarter was $4.9 million. On April 15, 2024, the Company paid a total of $1.4 million in cash dividends on the 8.625% Series A Cumulative Perpetual Preferred Stock (Nasdaq: XOMAP) and the 8.375% Series B Cumulative Perpetual Preferred Stock (Nasdaq: XOMAO). About XOMA CorporationXOMA is a biotechnology royalty aggregator playing a distinctive role in helping biotech companies achieve their goal of improving human health. XOMA acquires the potential future economics associated with pre-commercial and commercial therapeutic candidates that have been licensed to pharmaceutical or biotechnology companies. When XOMA acquires the future economics, the seller receives non-dilutive, non-recourse funding they can use to advance their internal drug candidate(s) or for general corporate purposes. The Company has an extensive and growing portfolio of assets (asset defined as the right to receive potential future economics associated with the advancement of an underlying therapeutic candidate). For more information about the Company and its portfolio, please visit www.xoma.com or follow the Company on LinkedIn. Forward-Looking Statements/Explanatory NotesCertain statements contained in this press release are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including statements regarding the timing and amount of potential commercial payments to XOMA and other developments related to VABYSMO® (faricimab-svoa), OJEMDA™ (tovorafenib), XACIATO™ (clindamycin phosphate) vaginal gel 2%, IXINITY® [coagulation factor IX (recombinant)], DSUVIA® (sufentanil sublingual tablet), and arimoclomol; the potential occurrences of the events listed under “Anticipated 2024 Events of Note”; the anticipated timings of regulatory filings and approvals related to assets in XOMA’s portfolio; and the potential of XOMA’s portfolio of partnered programs and licensed technologies generating substantial milestone and royalty proceeds over time. In some cases, you can identify such forward-looking statements by terminology such as “anticipate,” “intend,” “believe,” “estimate,” “plan,” “seek,” “project,” “expect,” “may,” “will”, “would,” “could” or “should,” the negative of these terms or similar expressions. These forward-looking statements are not a guarantee of XOMA’s performance, and you should not place undue reliance on such statements. These statements are based on assumptions that may not prove accurate, and actual results could differ materially from those anticipated due to certain risks inherent in the biotechnology industry, including those related to the fact that our product candidates subject to out-license agreements are still being developed, and our licensees may require substantial funds to continue development which may not be available; we do not know whether there will be, or will continue to be, a viable market for the products in which we have an ownership or royalty interest; if the therapeutic product candidates to which we have a royalty interest do not receive regulatory approval, our third-party licensees will not be able to market them; and the impact to the global economy as a result of the COVID-19 pandemic. Other potential risks to XOMA meeting these expectations are described in more detail in XOMA's most recent filing on Form 10-Q and in other filings with the Securities and Exchange Commission. Consider such risks carefully when considering XOMA's prospects. Any forward-looking statement in this press release represents XOMA's beliefs and assumptions only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. XOMA disclaims any obligation to update any forward-looking statement, except as required by applicable law. EXPLANATORY NOTE: Any references to “portfolio” in this press release refer strictly to milestone and/or royalty rights associated with a basket of drug products in development. Any references to “assets” in this press release refer strictly to milestone and/or royalty rights associated with individual drug products in development. As of the date of this press release, the commercial assets in XOMA’s milestone and royalty portfolio are VABYSMO® (faricimab-svoa), OJEMDA™ (tovorafenib), XACIATO™ (clindamycin phosphate) vaginal gel 2%, IXINITY® [coagulation factor IX (recombinant)], and DSUVIA® (sufentanil sublingual tablet). All other assets in the milestone and royalty portfolio are investigational compounds. Efficacy and safety have not been established. There is no guarantee that any of the investigational compounds will become commercially available. XOMA CORPORATION CONDENSED CONSOLIDATED BALANCE SHEETS (in thousands, except share and per share amounts) March 31, December 31, 2024 2023 ASSETS(unaudited) Current assets: Cash and cash equivalents$136,225 $153,290 Short-term restricted cash 160 160 Short-term equity securities 413 161 Trade and other receivables, net 3 1,004 Short-term royalty and commercial payment receivables 9,819 14,215 Prepaid expenses and other current assets 270 483 Total current assets 146,890 169,313 Long-term restricted cash 6,016 6,100 Property and equipment, net 40 25 Operating lease right-of-use assets 364 378 Long-term royalty and commercial payment receivables 65,577 57,952 Other assets - long term 533 533 Total assets$219,420 $234,301 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable$1,515 $653 Accrued and other liabilities 1,299 2,768 Contingent consideration under RPAs, AAAs and CPPAs 3,000 7,000 Operating lease liabilities 55 54 Unearned revenue recognized under units-of-revenue method 2,159 2,113 Preferred stock dividend accrual 1,368 1,368 Current portion of long-term debt 6,144 5,543 Total current liabilities 15,540 19,499 Unearned revenue recognized under units-of-revenue method – long-term 6,692 7,228 Long-term operating lease liabilities 319 335 Long-term debt 114,528 118,518 Total liabilities 137,079 145,580 Stockholders’ equity: Preferred Stock, $0.05 par value, 1,000,000 shares authorized: 8.625% Series A cumulative, perpetual preferred stock, 984,000 shares issued and outstanding at March 31, 2024 and December 31, 2023 49 49 8.375% Series B cumulative, perpetual preferred stock, 1,600 shares issued and outstanding at March 31, 2024 and December 31, 2023 — — Convertible preferred stock, 5,003 issued and outstanding at March 31, 2024 and December 31, 2023 — — Common stock, $0.0075 par value, 277,333,332 shares authorized, 11,636,355 and 11,495,492 shares issued and outstanding at March 31, 2024 and December 31, 2023, respectively 87 86 Additional paid-in capital 1,314,036 1,311,809 Accumulated deficit (1,231,831) (1,223,223) Total stockholders’ equity 82,341 88,721 Total liabilities and stockholders’ equity$219,420 $234,301 XOMA CORPORATION CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except share and per share amounts) Three Months Ended March 31, 2024 2023 Revenues: Revenue from contracts with customers$1,000 $- Revenue recognized under units-of-revenue method 490 437 Total revenues 1,490 437 Operating expenses: Research and development 33 54 General and administrative 8,461 6,196 Arbitration settlement costs - 4,132 Amortization of intangible assets - 225 Total operating expenses 8,494 10,607 Loss from operations (7,004) (10,170) Other income (expense) Interest expense (3,551) - Other income (expense), net 1,960 357 Net loss and comprehensive loss$(8,595) $(9,813) Less: accumulated dividends on Series A and Series B preferred stock (1,368) (1,368) Net loss and comprehensive loss attributable to common stockholders, basic and diluted$(9,963) $(11,181) Basic and diluted net loss per share attributable to common stockholders$(0.86) $(0.98) Weighted average shares used in computing basic and diluted net loss per share attributable to common stockholders 11,580 11,460 XOMA CORPORATIONCONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS(in thousands) Three Months Ended March 31, 2024 2023 Cash flows from operating activities: Net loss$(8,595) $(9,813)Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation expense 2,856 1,570 Common stock contribution to 401(k) 118 123 Amortization of intangible assets — 225 Depreciation 2 1 Accretion of long-term debt discount and debt issuance costs 306 — Non-cash lease expense 14 47 Change in fair value of equity securities (252) 24 Changes in assets and liabilities: Trade and other receivables, net 1,001 (5)Prepaid expenses and other assets 213 269 Accounts payable and accrued liabilities (105) 3,122 Operating lease liabilities (15) (50)Unearned revenue recognized under units-of-revenue method (490) (437) Net cash used in operating activities (4,947) (4,924) Cash flows from investing activities: Payments of consideration under RPAs, AAAs and CPPAs (15,000) (9,600)Receipts under RPAs, AAAs and CPPAs 7,771 2,366 Purchase of property and equipment (17) — Net cash used in investing activities (7,246) (7,234) Cash flows from financing activities: Principal payments – debt (3,616) — Debt issuance costs and loan fees paid in connection with long-term debt (581) — Payment of preferred stock dividends (1,368) (1,368)Repurchases of common stock (13) — Proceeds from exercise of options and other share-based compensation 1,956 — Taxes paid related to net share settlement of equity awards (1,334) — Net cash used in financing activities (4,956) (1,368) Net decrease in cash, cash equivalents and restricted cash (17,149) (13,526)Cash, cash equivalents and restricted cash at the beginning of the period 159,550 57,826 Cash, cash equivalents and restricted cash at the end of the period$142,401 $44,300 Supplemental Cash Flow Information: Cash paid for interest$3,780 $— Non-cash investing and financing activities: Accrual of contingent consideration under the Affitech CPPA$3,000 $— Preferred stock dividend accrual$1,368 $1,368 Investor contact: Media contact:Juliane SnowdenKathy VincentXOMAKV Consulting & Management+1-646-438-9754+1-310-403-8951juliane.snowden@xoma.comkathy@kathyvincent.com i https://www.takeda.com/newsroom/newsreleases/2024/takeda-announces-positive-topline-results-from-phase-2-study-evaluating-mezagitamab-TAK-079-a-potential-best-in-class-anti-CD38-monoclonal-antibody-for-primary-immune-thrombocytopenia/