Jazz Pharmaceuticals has signed a definitive agreement for the acquisition of Redx Pharma's pan-RAF inhibitor program for the potential treatment of RAF and RAS mutant tumors.
Redx will perform certain pre-clinical activities for the program under a separate collaboration agreement with Jazz. Jazz will be responsible for further development, regulatory activities and commercialisation.
Under the terms of the agreement, Jazz will pay Redx an upfront payment of $3.5 million. Redx is eligible to receive up to $203 million in development, regulatory and commercial milestone payments from Jazz, and incremental tiered royalties in mid-single digit percentage, based on any future net sales.
“We are excited to acquire Redx’s pan-RAF inhibitor program. It has the potential to work in RAF driven tumors where current selective B-RAF inhibitors and their respective combinations are ineffective due to acquired resistance mechanisms. In addition, there is the potential to address RAS driven tumors,” said Robert Iannone, M.D., M.S.C.E., executive vice president, research and development of Jazz Pharmaceuticals.
“We look forward to advancing the pan-RAF inhibitor program that is part of a novel class of next generation precision oncology drugs and is highly complementary to our growing R&D portfolio of early-stage, innovative, hematology/oncology therapies.”
Mutations leading to uncontrolled signalling via the RAS-RAF-MAPK pathway are seen in more than one third of all cancers. The pan-RAF inhibitor program aims to overcome resistance mechanisms associated with clinically approved B-RAF selective drugs.
The RAF kinases (A-RAF, B-RAF and C-RAF) are an integral part of this pathway, with B-RAF mutations commonly seen in the clinic. Although most B-RAF V600E mutant skin cancers are sensitive to approved B-RAF selective drugs, B-RAF V600E mutant colorectal cancers are surprisingly insensitive to these agents as monotherapy due to the functions of other RAF family members and require combination therapy.
B-RAF selective therapies fail to show clinical benefit against atypical B-RAF (non-V600E), other RAF and RAS driven tumors.
Pre-clinical study results of Redx’s pan-RAF program have demonstrated in vivo efficacy in a B-RAFV600E mutant colorectal cancer xenograft model as a single agent, where approved B-RAF selective drugs are ineffective as monotherapy. It has also shown promising activity in RAS-mutated cancer cells.
Jazz Pharmaceuticals已经签署了一份最终协议，收购Redx Pharma的pan-RAF抑制剂项目，用于治疗RAF和RAS突变肿瘤。
根据与 Jazz 的单独合作协议， Redx 将为该项目执行某些临床前活动。Jazz 将负责进一步的开发、监管活动和商业化。
根据协议条款， Jazz 将向 Redx 支付350万美元的预付款。根据未来的净销售额， Redx 有资格从 Jazz 获得高达2.03亿美元的开发、监管和商业里程碑付款，并以中个位数的百分比获得递增的分级版税。
“我们很高兴收购 Redx 的泛 RAF 抑制剂项目。它有可能在 RAF 驱动的肿瘤中起作用，目前选择性的 B-RAF 抑制剂及其各自的组合由于获得性耐药机制而无效。此外，还有可能解决 RAS 驱动的肿瘤，”医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士、医学博士爵士制药的研发。
“我们期待着推进 Pan-RAF 抑制剂项目，该项目是新一代精准肿瘤药物的一部分，与我们日益增长的早期、创新的血液学/肿瘤治疗的研发组合高度互补。”
通过 RAS-RAF-MAPK 途径导致无控制信号的突变在所有癌症中超过三分之一。泛 RAF 抑制剂计划旨在克服与临床批准的 B-RAF 选择性药物相关的耐药机制。
RAF 激酶（ A-RAF 、 B-RAF 和 C-RAF ）是该途径的一个组成部分，临床上常见的 B-RAF 突变。虽然大多数 B-RAF V600E 突变皮肤癌对批准的 B-RAF 选择性药物敏感，但 B-RAF V600E 突变结肠直肠癌由于其他 RAF 家族成员的功能，需要联合治疗，因此对这些药物的单一治疗作用惊人地不敏感。
B-RAF 选择性治疗未能显示对非典型 B-RAF （非 V600E ）、其他 RAF 和 RAS 驱动肿瘤的临床疗效。
Redx 泛 RAF 方案的临床前研究结果显示，在 B-RAFV600E 突变结肠直肠癌异种移植模型中，作为单一药物，经批准的 B-RAF 选择性药物作为单一药物无效。它在 RAS 突变的癌细胞中也显示出有希望的活性。