RYPLAZIM™(血纤维蛋白溶酶原)BLA审查程序更新 - PDUFA行动日期
Prometic首席运营官兼首席财务官Bruce Pritchard在评论2017年财务业绩时表示：“除了与SRAM应收账款相关的坏账有关的一项大规定外，我们2017年底的财务业绩一直保持季度 - 完成符合我们的预期，目标和更早的指导，我们已经稳定了我们的研发和行政，销售和市场营销支出的目标水平，并有针对性地投入了我们的商业基础设施，以期在商业上推出纤溶酶原和其他药物候选人。
PBI-4050(用于治疗Alström综合征) - Prometic宣布其口服活性铅的候选药物PBI-4050被欧洲委员会授予治疗Alström综合征(“ AS ”)的孤儿药物名称。该公司还宣布，PBI-4050已获得英国医药和保健品管理局(“MHRA”)颁发的用于治疗AS的有希望的创新医药(“PIM”)指定。美国食品和药物管理局已经为Promet的口服活性抗纤维化前导候选药物PBI-4050授予孤儿药物名称状态，用于治疗Alström综合征。
更新 ： Prometic在2018年3月28日报道了来自Alström综合征患者正在进行的PBI-4050研究的阳性临床数据。
PBI-4050(用于IPF) - Prometic获得FDA研究性新药(IND)批准，开始其口服抗纤维化前导药物候选物PBI-4050在患有IPF的患者中的关键性3期临床试验。美国食品及药物管理局授予PBI-4050快速通道名称，该候选人还获得英国药品和医疗保健产品管理局(MHRA)的有希望创新医学(PIM)指定为IPF患者nintedanib的附加治疗。
根据FDA的反馈，Prometic现在将进行“所有参与者研究”。入选标准将大大简化，因此研究将纳入轻度至中度IPF患者，无论患者是否采用nintedanib(OFEV [®])进行背景标准护理。因此，该研究将提供PBI-4050作为独立药物和作为nintedanib的附加药物的疗效数据，并将成为数据集的一部分，以支持一种简单，全面的指标“，用于治疗IPF”。患者将被随机分配接受安慰剂，或两剂PBI-4050(800 mg或1,200 mg)中的一种，共52周。中期分析将在26周进行。主要终点是年用力肺活量(FVC)下降率，在强制呼吸期间呼出的空气总量(以mL表示)并且测量超过52周(mL /年)。由于吡非尼酮与PBI-4050之间已知的药物相互作用，服用吡非尼酮的患者将被排除在外。
PBI-4050，PBI-4547和PBI-4425(中国开发和商业化) - 2017年8月，本公司与江苏融宇制药股份有限公司，南京融宇生物技术股份有限公司，关联公司签订了使用许可协议和合作协议深圳市皇家资产管理有限公司(统称“SRAM”)就其中小分子PBI-4050，PBI-4547和PBI-4425的中国使用权获得许可。
RYPLAZIMTM(血纤维蛋白溶酶原) - 用于治疗先天性纤溶酶原缺陷 - Prometic完成了其与纤维蛋白溶酶原生物制剂许可证申请(“BLA”)的申请，用于治疗先天性纤溶酶原缺陷患者。美国食品和药物管理局已将Prometic的纤溶酶原早期授予孤儿药和快速通道指定用于该指示。
Prometic公司发布了关于RYPLAZIM™(血纤维蛋白溶酶原)治疗先天性纤溶酶原缺陷症的关键性2/3期临床试验的新的长期临床数据。数据表明，在用RYPLAZIM TM(纤溶酶原)治疗总共48周的10位患者中，没有观察到病变复发，并且没有观察到与该长期给药相关的耐受性问题。Prometic之前曾报道过这一关键2/3期临床试验的数据，其中Prometic观察到RYPLAZIM TM(血纤维蛋白溶酶原)治疗一直替代并维持血浆中的纤溶酶原浓度达到足够的水平，并且所有10例患者治疗12周。在同样的关键2/3期治疗方案中，这10例患者已经治疗了36周，
美国食品和药物管理局授予Prometic RYPLAZIM [TM](血纤维蛋白溶酶原)用于治疗先天性纤溶酶原缺陷症患者的罕见小儿疾病名称。
美国食品和药物管理局接受了为其RYPLAZIM [纤维蛋白溶酶原]替代疗法提供Promet BLA的申请，并给予了优先审查状态并设定了2018年4月14日的处方药使用费法(PDUFA)。
更新： The current BLA filing includes the clinical data on 10 patients with 12 weeks of data for an accelerated regulatory pathway. Since filing the current BLA, Prometic has accumulated additional clinical data encompassing more than 3,200 infusions of RYPLAZIM™ (plasminogen) over treatment periods exceeding 48 weeks during which similar clinical activity and tolerability profiles, as previously reported, were observed. The original guidance from the FDA was for Prometic to submit such long-term clinical data in a supplemental BLA in order to secure full licensure in 2019. Full licensure would provide for the long-term efficacy and safety data to be included in the prescribing information of RYPLAZIM™ (plasminogen) which would further support Prometic's claims of the strong health economics benefit associated with the use of RYPLAZIM™ (plasminogen).
The FDA's review of the BLA raised no issues regarding the clinical data for the accelerated approval. The FDA has, however, identified the need for Prometic to make a number of changes in the Chemistry, Manufacturing and Controls (CMC) section of its BLA. These changes require the implementation and validation of additional analytical assays and "in-process controls" in the manufacturing process of RYPLAZIM™ (plasminogen). While Prometic is expecting to complete said implementation and validation in April 2018, it will be necessary to manufacture additional RYPLAZIM™ (plasminogen) lots to support the implementation and validation of these process changes. Prometic expects to complete the manufacturing of the additional validation lots in the summer of 2018 and anticipates being able to provide the FDA with such new CMC data for its review in the fourth quarter of 2018, which is beyond the Prescription Drug User Fee Act (PDUFA) date of April 14, 2018. The FDA requested that such CMC data be submitted as an amendment to the current BLA and has invited Prometic to also submit the long-term (48-week) clinical data at the same time instead of through the originally agreed upon supplemental BLA process. This process will allow the FDA to consider granting full-licensure under the current BLA. If granted, this is expected to allow a faster sales ramp-up from launch than could have been achieved had provisional licensure been obtained by the current PDUFA date. The Company continues to interact with the FDA and will provide a further update when it is in a position to disclose a new PDUFA date. The FDA indicated that the submission of the new CMC data will not impact the previously granted designations, including the Priority Review Status, the Orphan Drug Designation and the Rare Pediatric Disease Designation for RYPLAZIM™ (plasminogen) for the treatment of congenital plasminogen deficiency.
RYPLAZIM™ (plasminogen) - for IPF - Orphan drug designation status was granted to Prometic's RYPLAZIM™ (plasminogen) for the treatment of Idiopathic Pulmonary Fibrosis ("IPF") by the FDA. In an animal model that emulates pulmonary fibrosis in humans, Prometic's RYPLAZIM™ (plasminogen) performed favorably compared to recently- approved IPF drugs to treat this condition. We observed that RYPLAZIM™ (plasminogen) significantly reduced tissue scarring in the lungs, indicating the potential for providing clinically significant improvement and stabilization in lung function.
RYPLAZIM™ (plasminogen) – for Acute Lung Injury / Acute Respiratory Distress Syndrome - The Company presented new data at the 2017 American Thoracic Society (ATS) International Conference in Washington, D.C. demonstrating the benefits of plasminogen administration in reducing lung injury in a gold standard animal model of ALI/ARDS associated with acute pancreatitis.
Plasminogen - for Chronic Tympanic Membrane Perforation -The Company received approval by the Swedish Medical Products Agency to commence a clinical trial with its plasminogen therapy in patients suffering from chronic tympanic membrane perforation (chronic TMP). The is a dose escalation, randomized, placebo-controlled study designed to investigate the safety, feasibility and initial efficacy of local injections of a novel and proprietary plasminogen formulation for the treatment of chronic tympanic membrane perforation. Up to 33 adult patients are expected to be enrolled. The study is being conducted at a single center in Sweden, under the supervision of Cecilia Engmér Berglin, MD, PhD from the Department of Otorhinolaryngology at Karolinska University Hospital in Stockholm, Sweden. The Karolinska University Hospital is the second largest ear/nose/throat center in the world.
Plasminogen – for Diabetic Foot Ulcers - The Company received approval by the Swedish Medical Products Agency (MPA) Clinical Trial Application (CTA) to commence a Phase 2 clinical trial of its plasminogen therapy in patients suffering from diabetic foot ulcers (DFU). The Phase 2 clinical trial is a prospective, dose escalation study of the safety, feasibility and initial efficacy of subcutaneous plasminogen for the treatment of DFU in 20 adult subjects. The study is being conducted in one study center in Sweden, under the supervision of Dr. Jan Apelqvist, an expert in the field of diabetic foot ulcers and hard to treat wounds from the Department of Endocrinology, Division of Clinical Sciences at Skane University Hospital in Malmö, Sweden.
IVIG for Primary Immunodeficiency Disorder (PIDD) - The Company announced positive interim six-month clinical data from its ongoing pivotal IVIG Phase 3 clinical trial in patients suffering from primary immunodeficiencies (PID). Review of the data by the Data Safety Monitoring Board (DSMB) confirmed no significant safety issues and that clinical activity appeared to be comparable to existing commercial IVIG products. This data meets Health Canada's requirements for a New Drug Submission (NDS) filing with at least 20 evaluable PID patients treated with Prometic's IVIG for a minimum six-month period together with comparison data from a similar six-month period during which patients received comparable approved commercial IVIG products. Forty-nine adult and 10 pediatric patients have completed at least six months of treatment with Prometic's IVIG in the current trial. Comparisons with the approved products include safety, Immunoglobulin (IgG) levels, frequency of infections, use of antibiotics, periods of hospitalization due to severe infections and missed days of school or work.
These results from its pivotal IVIG Phase 3 trial will enable Prometic to complete the clinical portion of its New Drug Submission with Health Canada.
Update: The ongoing non-inferiority phase 3 clinical trial for IVIG in adults, required for the filing of a BLA in the USA, is expected to be completed in the first quarter of 2018 followed by the pediatric cohort completion in the first quarter 2019.
INTER ALPHA-ONE INHIBITOR PROTEINS (IAIP) - for the treatment of Necrotising Enterocolitis in Neonates (NEC) a condition that accounts for approximately 19% of the US's annual neonatal medical expenditures as well as an estimated $5 billion in annual hospitalization costs in the US.
Update: The Company received from the FDA a Rare Pediatric Disease Designation for its IAIP for the treatment of NEC. In addition to the Rare Pediatric Disease Designation, IAIP was also granted an Orphan Drug Designation by the FDA in February 2018.
Bioseparation Technologies Highlights:
The Company received a $9.5 million purchase order for the supply of affinity resin to an existing client, a global leader in the biopharmaceutical industry. This purchase order is part of an ongoing license and long-term supply agreement previously secured with the client. Supply of the affinity resin (manufactured by Prometic at its Isle of Man facility) to the client began in the second half of 2017 and will continue throughout 2018. Prometic's client is using the resin for large-scale purification of a therapeutic protein product manufactured in large quantities.
Prometic closed a $53.1 million bought deal equity offering of common shares through the syndicate of underwriters led by Cantor Fitzgerald Canada Corporation as the lead underwriter and sole bookrunner, and including RBC Dominion Securities Inc., National Bank Financial Inc., Scotia Capital Inc., Desjardins Securities Inc. and Echelon Wealth Partners Inc. Prometic issued 31,250,000 common shares of at a price of $1.70 per share for gross proceeds of $53.1 million. In addition, Prometic completed a concurrent, non-brokered private placement of 5,045,369 common shares of at a price of $1.70 per common share (the "Private Placement") with Structured Alpha LP ("SALP"), an affiliate of Peter J. Thomson's investment firm, Thomvest Asset Management Inc. following the exercise by SALP of its pre-emptive right to participate in any future public offering of Prometic's common shares. The $8.6 million in proceeds from the Private Placement were used to offset and reduce the total amount owed by Prometic to SALP pursuant to the previously mentioned Loan entered into in April, 2017.
Prometic closed the previously mentioned USD $80 million (CAD $100 million) credit facility with SALP. As partial consideration for establishing the credit facility, Prometic granted SALP an initial 10 million warrants with an exercise price of CAD $1.70 per common share with a term expiring June 30, 2026, alongside an additional 44 million warrants at the same exercise price and term, which will vest in tranches each time Prometic draws an additional amount of USD $10 million (CAD $12.5 million) under the Credit Facility. Drawing on the first 4 tranches of USD $10 million (CAD $12.5 million) would each cause 5 million warrants to vest, whereas drawing on the second set of 4 tranches of USD $10 million (CDN $12.5 million) would each cause 6 million warrants to vest. All amounts drawn from the credit facility will bear interest of 8.5% per annum and the principal will be repayable on November 30, 2019.
2017 Year-End Financial Results
Total revenues for the year ended December 31, 2017 were $39.1 million compared to $16.4 million for the year ended December 31, 2016. Revenues from milestones and licensing revenues for the year ended December 31, 2017 were $19.7 million; there were no milestones and licensing revenues for the year ended December 31, 2016.
The Company incurred a net loss of $120.0 million during the year ended December 31, 2017 compared to a net loss of $110.7 million in 2016, representing an increase in the net loss of $9.3 million.
The Company incurred total R&D costs of $100.4 million during the year ended December 31, 2017 compared to $87.6 million during the year ended December 31, 2016. R&D expenses include the manufacturing cost of plasma-derived and small molecule therapeutics to be used in clinical trials and other R&D purposes. The manufacturing cost of these therapeutics represents approximately $34.0 million of the $100.4 million in R&D expenses during the year ended December 31, 2017 and $33.2 million of the $87.6 million in R&D expenses during the year ended December 31, 2016. This represents an increase of $0.8 million during the year ended December 31, 2017 compared to the corresponding period in 2016.
Other R&D expenses, excluding the manufacturing cost of therapeutics to be used in R&D activities discussed above, were $66.4 million during the year ended December 31, 2017 compared to $54.4 million for the corresponding period in 2016, representing an increase of $12.0 million. The increase is partially due to higher salary and benefit expenditures by approximately $6.4 million reflecting the increase in employees working on the clinical trials and at our research centers. In addition, Contract Research Organizations ("CRO") and investigator expenses incurred in relation to the clinical trials and pre-clinical activities increased by $2.3 million reflecting the increase in the number of trials in progress, the duration and higher patient enrolment of the trials.
Administrative, selling and marketing expenses amounted to $31.4 million during the year ended December 31, 2017 compared to $28.5 million during the year ended December 31, 2016. The increase is mainly attributable to the increase in consulting expenses of $3.0 million incurred in relation to the preparation for the plasminogen launch.
2017 Fourth Quarter Financial Results
Total revenues for the fourth quarter ended December 31, 2017 were $6.6 million compared to $4.1 million for the fourth quarter ended December 31, 2016. Revenues from the sale of goods amounted to $5.5 million for the fourth quarter ended December 31, 2017, compared to $3.3 million for the quarter ended December 31, 2016. There were no milestones and licensing revenues for the fourth quarters of either 2017 or 2016.
R&D expenses remained stable at $28.2 million during the quarter ended December 31, 2017 compared to $28.0 million for the corresponding period in 2016.
Administrative, selling and marketing expenses amounted to $8.7 million during the fourth quarter of 2017, compared to $12.0 million for the quarter ended December 30, 2016 representing a decrease of $3.2 million due mainly to the severance, salary and benefit expenditures of $2.1 million in rationalization efforts at Telesta following the acquisition in the last quarter of 2016.
Bad debt expense
Bad debt expense was $20.5 million during the year and the quarter ended December 31, 2017 compared to $0.8 million for the corresponding periods in 2016, representing an increase of $19.7 million. The current year expense is due to the write-off, affecting the fourth quarter of 2017, of the amounts due in regards to a license agreement. The licensee having not remitted funds associated with the license fee and initial milestone payment within the specified payment terms was consequently in breach of the agreement. As a result, the Company was in a position to exercise its contractual rights and opted to terminate the agreement in March 2018, thereby returning all the rights previously conferred under the license agreement back to Prometic.
Conference Call Information
Prometic will host a conference call at 8:00 am (ET) on Thursday March 29, 2018. The telephone numbers to access the conference call are (647) 427-7450 and 1-888-231-8191 (toll-free). A replay of the call will be available from Thursday March 29, 2018 at 10:00 am until April 5, 2018. The numbers to access the replay are 1-416-849-0833 (passcode:9793595) and 1-855-859-2056 (passcode:9793595). A live audio webcast of the conference call, with slides, will be available through the following : https://event.on24.com/wcc/r/1641885/F1524EE1A546B03D77815DB3A675E180
Additional Information in Respect to the Fourth Quarter and Year ended December 31, 2017
Prometic's MD&A and 2017 consolidated financial statements for the quarter and year ended December 31, 2017 will be filed on SEDAR (http://www.sedar.com) and will be available on the Company's website at www.prometic.com.
About Prometic Life Sciences Inc.
Prometic Life Sciences Inc. (www.prometic.com) is a biopharmaceutical corporation with two drug discovery platforms focusing on unmet medical needs in the field of fibrosis and orphan diseases. The first platform, small molecule therapeutics, stems from the discovery of two receptors GPR40/GPR84 acting as dual master-switches which are at the core of the healing process as opposed to fibrosis. The second platform, plasma-derived therapeutics, leverages Prometic's vast experience in bioseparation technologies to address unmet medical needs with therapeutic proteins not currently commercially available, such as RYPLAZIM™ (plasminogen). Prometic is also leveraging the second platform higher recovery yield advantage to develop some more established plasma-derived therapeutics with significant growth in demand such as Intravenous Immunoglobulin (IVIG) and provides access to its proprietary bioseparation technologies to enable pharmaceutical companies in their production of non-competing biopharmaceuticals. Globally recognized as a bioseparations expert, the Corporation derives revenue from this activity through sales of affinity chromatography media which contributes to offset the costs of its own R&D investments. Headquartered in Laval (Canada), Prometic has R&D facilities in the UK, the U.S. and Canada, manufacturing facilities in the UK and commercial activities in the U.S., Canada, Europe and Asia.
Forward Looking Statements
This press release contains forward-looking statements about Prometic's objectives, strategies and businesses that involve risks and uncertainties. These statements are "forward-looking" because they are based on our current expectations about the markets we operate in and on various estimates and assumptions. Actual events or results may differ materially from those anticipated in these forward-looking statements if known or unknown risks affect our business, or if our estimates or assumptions turn out to be inaccurate. Such risks and assumptions include, but are not limited to, Prometic's ability to develop, manufacture, and successfully commercialize value-added pharmaceutical products, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of Prometic to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. You will find a more detailed assessment of the risks that could cause actual events or results to materially differ from our current expectations in Prometic's Annual Information Form for the year ended December 31, 2017, under the heading "Risk and Uncertainties related to Prometic's business". As a result, we cannot guarantee that any forward-looking statement will materialize. We assume no obligation to update any forward-looking statement even if new information becomes available, as a result of future events or for any other reason, unless required by applicable securities laws and regulations. All amounts are in Canadian dollars unless indicated otherwise.