PledPharma AB Creating value within treatment of life-threatening diseases

Transcription

1 PledPharma AB Creating value within treatment of life-threatening diseases PledOx : A cure for chemotherapy-induced peripheral neuropathy (CIPN)? Jacques Näsström, PhD, MBA, CEO BIO-Europe 2014 November 3 November 5 Frankfurt, Germany

2 PledPharma is a Swedish pharma company looking to partner PledOx, their lead asset About PledPharma Swedish pharma company with emphasis on oxidative stress and life-threatening diseases Lead compound: PledOx for prevention of severe chemotherapy induced side-effects Projects for other life-threatening diseases in development Clinically established and proven class of compounds Reduced clinical and regulatory risk Favorable patent situation Listed on NASDAQ OMX First North (STO:PLED) 1

3 An estimated 1.7M patients are eligible for platinumand taxane- based chemotherapy in the US, EU5 and JP each year SIZE OF PATIENT POPULATION ADDRESSABLE BY ASSET Thousands of Patients Tumor Incidence 1 # Cycles of Chemotherapy Agents 2 US EU5 JP CRC Pancreatic Breast Lung Ovarian Millions of Cycles 3,5 3 2,5 2 1,5 1 0,5 0 US EU5 JP Oxaliplatin Cisplatin Paclitaxel Carboplatin Docetaxel PledOx is administered per cycle of chemotherapy as a pre-treatment and has demonstrated efficacy in a broad range of tumor types and chemotherapy regimens (PledOx is expected to have efficacy in all tumors/regimens shown above) 1 Sources: SEER, EUCAN, GLOBOCAN 2 Sources: IMS Data on unit sales of chemotherapy agents with regimen assumptions applied; no data for cisplatin in JP 2

4 Many of these patients suffer from a variety of side effects and dose-limiting toxicities Side Effect Neuropathy CIPN Thrombocytopenia Febrile Neutropenia Neutropenia Diarrhea Nausea/ Vomiting Unmet Need Commentary Often have to reduce/discontinue treatment Can have long-term effects Limited treatment options, dose-limiting Treatable with antibiotics, G-CSFs Severity and high cost of complications keep it topof-mind with payers and prescribers G-CSFs can manage, but pre-treatment is restricted to certain patient populations Dose-limiting Can be dose-limiting Used to be major problem, better controlled now High; no current tx options Chemotherapy can be reduced, postponed, or even completely discontinued if severe side effects persist Can lead to suboptimal treatment results Affects quality of life Huge medical need for preventive treatment of chemotherapy induced side-effects Medium; somewhat manageable with current tx options Low; manageable with current tx options 3

5 In particular, neuropathy has no available treatments and lead to treatment modification Current Standard of Care for Neuropathy Management Intervention Commentary TCA, pregabalin and gabapentin None are approved for neuropathy; only manage symptoms Ca-Mg infusion Treatment modification or discontinuation This intervention was formerly commonly used (as much as by 50% of physicians) No longer recommended due to definitive study by Loprinzi et al., ASCO June 2013 About 40% of patients discontinue due to neurotoxicity; negatively affects patient outcomes Source: Gramont et. al. JCO 2000 There is a high unmet need for neuropathy treatment given nothing else is available 4

6 PledOx aims to be a standard pretreatment to chemotherapy treatment PledOx will become a standard addition to prevent severe chemotherapy-induced sideeffects of chemotherapy, including : - Neuropathy - Neutropenia - Thrombocytopenia Huge potential for use with a range of chemotherapies and cancer types More efficacious and broader effect than existing treatments Unique mechanism of action PledPharma goal: maximizing the value of PledOx to patients and shareholders Sources: Leonard et al, BMC Cancer. 2005; 5: 116; American Cancer Society 5

7 PledOx has a unique mechanism of action as a superoxide dismutase mimetic 3000 ESR Spectra Control HX + XO O DMPO Signal intensity Mangafodipir HX + XO O DMPO mangafodipir Signal intensity Magnetic field (G) Magnetic field (G) H 2 O 2 Mitochondrial manganese superoxide dismutases (MnSOD) defend cells against damage due to oxidative stress under normal circumstances Superoxide dismutase mimetics bolster the body s ability to fend off damage due to pathological oxidative stress caused by chemotherapy Manganese-based SOD mimetics like mangafodipir and PledOx act as catalytic antioxidants since manganese can cycle between Mn 2+ ó Mn 3+ - dismutating free-radicals without being consumed These compounds are furthermore potent iron chelators which contribute to their cytotoxic effect on cancer cells Sources: Brurok H, et al. Biochem Biophys Res Commun.1999; Miriyala S et al., Biochimica et Biophysica Acta

8 Clinical development prompted a rational transition of lead compounds from mangafodipir to PledOx MANFOL I study: phase IIa study in colorectal cancer patients: Mangafodipir All further studies: PledOx Clinically proven MRI contrast medium, previously marked but withdrawn due to commercial reasons A low Molecular Enzyme Mimetic (lowmem), MnSOD and iron chelator Strong safety profile (based on >200,000 patients treated with mangafodipir) Rational chemical modification Developed from mangafodipir, but with potential for better efficacy and better safety At equivalent Mn 2+ doses, PledOx was found to be at least 10x more potent than mangafodipir Completed dose-escalation in ongoing Phase IIb trial showed no safety or toxicity issues Pending composition of matter patent until

9 PledOx has a strong preclinical data package demonstrating cytoprotection and anti-tumor activity PledOx protects cells and preserves/enhances the anti-tumoral effect of chemotherapy: PLED compounds are cytotoxic on cancer cells (Fig 7 Karlsson et al. 2012) Manganese containing PLED compounds protect against chemotherapy induced myelosuppression across a range of structurally diverse chemical classes of chemotherapies: taxanes (docetaxel and paclitaxel), pyrimidine analogues (5-FU), anthracyclines (doxorubicin) and platinums (carboplatin and oxaliplatin) (see bolded examples on the bottom right) The anti-tumour activity of the chemotherapy is not compromised but rather potentiated by the PLED compounds (Karlsson et al. 2012, top right graph) W B C 1.2 p = c o n tro ls o x a lip la tin m g /k g c a lm a n g a 6.5 m m o l/k g + o x a l Sources: Alexandre J, et al., Journal of the National Cancer Institute, 2006; Kurz T, et al., Translational Oncology 2012, Laurent A, et al. Cancer Research, 2005, Karlsson JO, et al. Translational Oncology 2012 as well as PledPharma patent applications. 8

10 Pled compound has clinical data demonstrating statistically significant reduction in grade 3/4 AEs MANFOL Clinical Study Design 14 patients with metastatic colorectal cancer Scheduled for 12 treatment cycles with FOLFOX During the first 3 cycles the patients received pretreatment with placebo or the PLED-derivative mangafodipir (18 total placebo cycles, 20 total mangafodipir cycles) Number of adverse events registered according to National Cancer Institute s scale Clinical Study Results Note the lack of grade 3/4 AEs in treated patients 9

11 PledOx is currently in Ph2 PLIANT trial and expects results to read out in Q PledOx Development Program Discovery Pre-clinical Phase I Phase II Regulatory Approval US/ EU Market Launch PLIANT trial: PledOx (calmangafodipir) is being tested in a large international phase IIb study in patients with colorectal cancer treated with chemotherapy FOLFOX Results read out Q Primary endpoint: neutropenia, or reduction in white blood cells (neutrophils) Secondary endpoints include: Peripheral sensory nerve damage (CIPN) Infection due to loss of white blood cells (febrile neutropenia) Recruitment update: All165 patients recruited Results update: Third and final safety analysis after 90 patients passed No grade 2 or worse neuropathy side effects seen within dose escalation population receiving FOFOX with or without addition of bevacizumab 10

12 Promising preliminary data indicates effect with PledOx on CIPN - from unblinded part 1 C IP N P a tie n ts w ith o u t g r a d e 2 o r w o r s e n e u r o p a th y (% ) A ll P le d O x d o s e s c o m b in e d w ith a t le a s t 7 c y F O L F O X (n = 9, 5 w ith b e v a c iz u m a b ) L o p rin z i e t a l J C I C y c le CIPN as rated with the NCI Sanofi oxaliplatin scale # of patients (%) without grade 2 or worse neuropathy Nine out of 11 part 1 patients completed at least 7 cycles with FOLFOX after pre-treatment with PledOx; 2 µmol/kg (n=1), 5 µmol/kg (n=3 all with bevacizumab, 10 µmol/kg (n=5) two with bevacizumab None of these patients displayed any grade 2 or worse neuropathy Comparison with literature data from Loprinzi et al. 2013, JCI

13 PledPharma has a unique and robust IP portfolio Four granted patent families Basic patents in 2017, EP, US and JP Two additional in 2018, EP and US Use of PLED-derivatives as pharmaceuticals for the treatment of oxidative stress related conditions Three patent applications/patents Anticancer effect of certain PLED derivatives, 2028, PCT application in national phase with approved US, Japanese, Chinese, Hong Kong and Russian patent plus a US CIP (continuation in part) Manganese and non-manganese compositions and broad therapeutic use of these new compositions, 2030, PCT application in national phase with approved South African patent Composition of matter, manufacturing process and broad therapeutic use of PledOx, end-2032, PCT Trademarks PledOx registered trademark in EU, US, Switzerland, Australia, Norway and Japan as well as pending in China and Russia 12

14 PledOx represents an attractive licensing opportunity Attribute PledOx Huge commercial opportunity Substantial market size ü Favorable pricing potential High clinical unmet need Strong uptake expected ü Full reimbursement and broad access Strong intellectual property protection through 2032 De-risked safety profile Defined patient population Completely unique MoA in a therapeutic area with limited competition from in-line or pipeline products ü ü ü ü ü 13