PledPharma. Carnegie Healthcare Seminar 14 March, Nicklas Westerholm, CEO

Transcription

1 PledPharma Carnegie Healthcare Seminar 14 March, 2018 Nicklas Westerholm, CEO 1

2 CEO & President Nicklas Westerholm PledPharma CMO Stefan Carlsson VP Product Strategy and Development Christian Sonesson Founded: 2006 Permanent Employees: 7 CSO Jacques Näsström CFO Yilmaz Mahshid Listed: Market cap*: Nasdaq First North Cash position (Q4 2017): ~620 mkr Location: CMC Sven Jacobsson Project Director & Reg Affairs Malin Nittve 310 mkr Stockholm Project Director Aladote Dennis Henriksen Clinical Project Director Marie Bengtsson 2 *

3 PledPharma 2018 Priorities building on key deliverables H Start recruitment of patients in PledOx Phase III studies Expand PledOx Phase III studies to Asia Deliver development strategy for Aladote 3

4 PledPharma s drug candidates in clinical development PledOx (calmangafodipir) (Phase 3) Prevents nerve damage caused by chemotherapy treatment in colorectal cancer patients Aladote (calmangafodipir) (Phase 1b/2a) Prevents acute liver failure caused by paracetamol (acetaminophen) poisoning 4

5 Colorectal Cancer (CRC) is the 3 rd most diagnosed cancer and standard treatment is associated with neuropathy ~ 700K patients (EU5, US, Japan) is drug treated for CRC yearly Oxaliplatin is associated with dose limiting and debilitating toxicities Oxaliplatin based chemotherapy is standard of care in both metastatic (stage IV) and adjuvant (stage III) patients % of patients get peripheral neuropathy during and up to 3 months after chemotherapy 20-30% of patients with symptoms >7 years post chemotherapy 5

6 6 No approved drug for prevention or treatment of Chemotherapy Induced Peripheral Neuropathy

7 PledOx PledOx aims to become new standard of care Chemotherapy Prevention of chemotherapy induced peripheral neuropathy + without negative impact on the efficacy of chemotherapy Easy to administrate as pre-treatment to chemotherapy 7

8 PledOx Phase 3 program Two double-blind, randomised, placebo controlled studies: POLAR-M (Metastatic CRC): 300 patients in US and EU undergoing chemotherapy (FOLFOX). PledOx with the doses 2 μmol/kg respective 5 μmol/kg vs placebo. POLAR-A (Adjuvant CRC): 200 patients in EU undergoing chemotherapy (FOLFOX). PledOx with the dose 5 μmol/kg vs placebo. Two complementary studies: POLAR-A provides CIPN evaluation in a homogenous population. POLAR-M is central to confirm that PledOx has no detrimental effect on chemotherapy. Primary endpoint Based on patient reported symptoms using the validated FACT/GOG-Ntx* instrument Assessed 9 months after first dose of chemotherapy Survival data Impact on progression free survival (PFS; POLAR-M), overall survival (OS; POLAR M) and disease free survival (DFS; POLAR A) assessed after 1 and 2 years (and 3 years for OS) Timelines First Patient In H PledPharma expects existing funds to cover delivery of top-line results, anticipated during * FACT/GOG-Ntx is a validated, relevant & sensitive patient reported outcome instrument for scoring, analysis and interpretation of neuropathy in a disease specific target patient population used in ~6,700 patients in 34 studies

9 PledOx Asia deal structure & Expansion of Phase III to Asia PledOx for Chemotherapy Induced Perepheral Neuropathy (CIPN) Colorectal cancer License to develop and commercialize PledOx in Japan, China, Hong Kong, Macau, South Korea, and Taiwan. Solasia will pay upfront, development, regulatory and sales milestones of up to 83 MUSD (approximately 700 MSEK)*. Upfront milestone of ~1 MUSD received in Dec-17. Solasia will pay industry standard royalty rates on sales applicable for an in licensed asset in Phase III development. Solasia will also fully finance an expansion of the Phase III program (POLAR-A and POLAR-M) to include Asian patients subject to regulatory consultations. The Phase I study in Japanese and Caucasian Healthy Volunteers with focus on safety, pharmacokinetics and tolerability showed positive results. Fully financed by Solasia. 9 * JPY 9,3 billion 9

10 Key value drivers of Asia licensing agreement Partnership with Solasia and its capabilities 3-4 years of accelerated development in Asia Milestones & Royalties Expansion of Phase 3 program will further enhance robustness 10

11 PledOx development timelines Calmangafodipir composition of matter patent expires 2018 Phase 1 study JPN completed POLAR CTA approved in US & UK Asian expansion of POLAR studies First patient in POLAR studies (H2)* 2020 Top line results of primary endpoint (CIPN) and key safety endpoints (1 year PFS/OS/DFS) All patients treated 2021 Regulatory submissions start 11 * First patient in delayed due to delay in delivery of study drug

12 12 PledOx Business Opportunity

13 Colorectal Cancer Common treatment approaches Stage I & II Surgery +/- RT Surgery + systemic therapy +/- RT (high-risk patients) Stage III (Adjuvant) Surgery + systemic therapy +/- RT Stage IV (Metastatic) Systemic therapy +/- RT Surgery + systemic therapy +/- RT (resectable disease) In early stages of disease, surgery has a high cure rate; many patients do not require additional systemic therapy Common Systemic Therapies: FOLFOX CAPOX Capecitabine 1L: FOLFOX + bevacizumab FOLFIRI + bevacizumab FOLFOX 2L (dictated by 1L therapy): While markets vary, FOLFOX +/- targeted therapy is the most commonly used first-line cytotoxic regimen for the systemic treatment of both Stage III and Stage IV CRC FOLFIRI or FOLFOX + bevacizumab FOLFIRI FOLFIRI + cetuximab (KRAS+) or aflibercept KEYTRUDA (MSI-H or dmmr) 13 CAPOX, capecitabine + oxaliplatin; FOLFIRI, 5-FU + leucovorin + irinotecan; FOLFOX, 5-FU + leucovorin + oxaliplatin 3L: Regorafenib Capecitabine Panitumumab (KRAS+)

14 Chemotherapy Induced Peripheral Neuropathy - Competitive landscape Common Treatment Approaches for CIPN CIPN Emerging Treatments Prevention No approved drug for prevention or treatment of Chemotherapy Induced Peripheral Neuropathy E (Sigma-1 Receptor) Mundipharma Ph 2 results published PledOx PledPharma Treatment of Symptoms Duloxetine (Cymbalta ) Tricyclic Antidepressants ART-123 (Thrombin [Coagulation Factor IIa]) Asahi Kasei Pharma Japanese development Gabapentin Pregabalin (Lyrica ) Phase II Phase III 14

15 PledOx Market Research, Pricing & Reimbursement Physicians and Payers expressed high interest in PledOx as a preventive treatment for CIPN. Payer clinical evidence needs forms strategy for Phase 3 data collection CIPN market research with US and EU Oncologists and Payers to gain insight and validation Confirms unmet needs in CIPN Verifies PledOx Target Product Profile Pricing assumption based on basecase target product profile 1000 USD/cycle 15 * Oncologists from US and EU3. Payers from US (National MCO, Regional HMO, Medicare, Academic/Integrated System) and EU3.

16 PledOx Commercial potential in CRC patients Drug treated CRC patients in US, EU5 & JPN/year ~700k Number of oxaliplatin treated patients in US, EU5 & JPN/ /year ~225k Number of oxaliplatin cycles in US, EU5 & JPN /year ~1.5 M Pricing assumption COGS assumption 1000 USD/cycle Low single digit percent 16

17 PledOx Summary and Opportunities Prevents nerve damage caused by chemotherapy treatment in colorectal cancer patients Development status: Phase 2 data provide reason to believe in Phase 3. First patient in POLAR Phase 3 studies in H Asian expansion of Phase 3 in 2018, subject to regulatory consultations Top-line results in POLAR-studies expected 2020 with regulatory submissions starting in Business opportunity: CRC 3rd most diagnosed cancer ~1,5M cycles of oxaliplatin yearly (US, EU5, JPN) High incidence of CIPN (40-60%) in CRC patients. CIPN can lead to discontinuation of cancer treatment % of patients with symptoms >7 years later No available prevention or treatment/ very limited competition Pricing and Reimbursement Research suggests a basecase pricing of 1000 USD/cycle Asia development will further realise PledOx global commercial potential 17 with opportunities for life-cycle management in to other indications based on its mechanism of action

18 PledPharma s drug candidates in clinical development PledOx (calmangafodipir) (Phase 3) Prevents nerve damage caused by chemotherapy treatment in colorectal cancer patients Aladote (calmangafodipir) (Phase 1b/2a) Prevents acute liver failure caused by paracetamol (acetaminophen) poisoning 18

19 Paracetamol (acetaminophen) poisoning has no adequate treatment if arriving late at hospital 19 bn units of paracetamol packages sold every year in the US. Minimum toxic dose of paracetamol in adults only 7.5g ~50 % of overdoses are unintentional cases of paracetamol overdose in US per year cases of paracetamol overdose in UK per year Could lead to acute liver failure, liver transplant or death ~ 25% of patients are late arrivals to hospitals (>8h) with no adequate treatment 19

20 Acetylcysteine (NAC) Standard of Care treatment Aladote Prevents acute liver failure caused by paracetamol (acetaminophen) poisoning No well-functioning treatment for patients who arrive more than 8 hours after ingestion Effective up to ~8h after overdose Overdose Time -> Acetylcysteine (NAC) Intensive care Liver transplantation Death Aladote 20

21 ALT levels U n it/l Aladote pre-clinical data provides reasons to believe underpins current clinical study Pre-clinical data presented at AASLD October 2017 F ig 5. N A C v s. C a M N-acetylcysteine and Aladote (CaM) Treatment-time post paracetamol overdose Ongoing Phase 1b/2a Study Randomized Phase 1b/2a in paracetamol overdosed patients * N S Three Aladote doses versus placebo as add-on to NAC regime A P A P C o n tr o l *** N A C 1 h N A C 2,5 h N A C 3 h *** C a M 2 h C a M 3 h *** *** C a M 6 h *** significant vs control Safety and tolerability Exploratory efficacy biomarkers for liver status 21

22 Aladote Summary and Opportunities Prevents acute liver failure caused by paracetamol (acetaminophen) poisoning Development status: Published Pre-clinical data supports ongoing Ph1b/2a study Ph1b/2a study results expected during H Development strategy TBD based on Ph1b/2a data, regulatory interactions and Scientific Advisory Board. Business opportunity: Paracetamol poisoning is a life-threatening condition. ~ 80K cases per year in US and UK respectively. Limited effect of standard of care for late-arrivals, ~ 25% of patients. 22

23 Significant shareholder value driving milestones and news flow* PledOx Results PI Study JPN POLAR CTA approved in US & UK Approval of further CTA applications FPI (POLAR-M and -A) Asian expansion of POLAR studies Patient inclusion status All patients included (POLAR-M and POLAR-A) DSMB decisions Top line results (POLAR- M and POLAR-A) 1Y PFS, OS and DFS data in both studies Regulatory submissions start Results Phase 1b/2a Development strategy TBD Aladote 23 *All timelines are current best estimates and may be subject to changes

24 24 PledPharma