Half-Year report January-June 2020

PledOx®
· PledPharma decided to prematurely stop and read-out the POLAR phase III program with a data cut-off targeted for the third quarter 2020. The decision was taken after a recommendation from the independent Drug Safety Monitoring Board (DSMB) to stop the studies due to a few severe allergic reactions after repeated dosing
· Positive pre-clinical results presented at Peripheral Nerve Society’s annual meeting
 
Aladote®
· Interactions are ongoing with the regulatory agencies to finalize specific details for the pivotal phase II/III study
 
Other
· PledPharma received US patent for method of treatment related to calmangafodipir
· CFO Yilmaz Mahshid has taken on a new external role and will be leaving PledPharma in September. Marie-Louise Alamaa has been appointed as interim CFO
 
Significant events after the reporting period
· Positive pre-clinical results with PledOx published in Antioxidants
· Marie Ekström Trägårdh  has chosen to step down from company’s Board of Directors due to personal reasons

Comments from the CEO
 PledOx POLAR program
In April, we took the decision to prematurely stop the clinical Phase III program POLAR with our lead candidate PledOx®, developed to provide patients that are treated adjuvantly or for metastatic colorectal cancer prevention against the nerve damage that can occur in conjunction with chemotherapy treatment. The decision was taken after a recommendation from the independent Drug Safety Monitoring Board (DSMB) to stop the program due to a few severe allergic reactions which has been observed in the studies after repeated dosing with study drug. Allergic hypersensitivity reactions are not uncommon in relation to platinum-based chemotherapy.
We will now concentrate on collecting the remaining data in the challenging COVID-19 environment and have targeted a data cut-off for the third quarter. The total Phase III data generated in the POLAR program will enable a thorough evaluation of the safety and efficacy and an assessment of the benefit/risk of PledOx. This evaluation will determine if further activities to find a path forward for PledOx to treat nerve damage associated with chemotherapy are motivated.

Continued scientific interest for PledOx
Despite this setback, we continue to gain interest for PledOx in the scientific community. In June, positive pre-clinical results with PledOx were presented as a poster at 2020 Annual Meeting of Peripheral Nerve Society (PNS). The preclinical oxaliplatin study confirms a protective effect of PledOx (calmangafodipir) against oxaliplatin-induced small fiber neuropathy. The administration of PledOx at the dose of 5 mg/kg prevents oxaliplatin-induced mechanical allodynia, cold hyperalgesia and reduction in intraepidermal nerve fiber density.
In early July, these pre-clinical results were also published in the peer-reviewed, open access journal Antioxidants. The article, titled Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity, focuses on the protective effect against oxaliplatin-induced peripheral neuropathy at the pathological level, and the findings are in line with the behavioral results.

US patent related to calmangafodipir
In May, we received a US patent for method of treatment related to calmangafodipir, forming an additional protective layer around both PledOx and Aladote. The expiry date for the patent is July 2030. This is in addition to the already granted composition-of-matter patent of calmangafodipir with expiry date December 2032. We are pleased with the notice of allowance of our second patent application to further strengthen our robust patent portfolio.

Continued development of Aladote
Our focus on Aladote and the ongoing regulatory interactions and clinical study remains unchanged as Aladote represents an important opportunity to address the high unmet medical need following paracetamol intoxication. A Phase I/IIa Proof-of-Principle study has been successfully completed, and a pivotal phase II/III study with a single administration is under planning. It is reassuring that no severe allergic-hypersensitivity reactions have been reported after single administration in the clinical trials with calmangafodipir.
In order to continue the development of our clinical portfolio, we have a robust cash position of approximately 184 million SEK in cash and cash equivalents reported at the end of the second quarter 2020.

Changes in management team and Board
In late May, we announced that CFO Yilmaz Mahshid has decided to leave the company and take on the position as CEO of Medivir. I have worked closely with Yilmaz during an intense period for the company, and I am very grateful for his commitment and professionalism. I wish him the best of success with his future commitments. In June, we named Marie-Louise Alamaa as the new interim CFO at PledPharma. She has extensive experience within finance and controlling from public companies, and she will make an excellent addition to the team. After the period, Board member Marie Ekström Trägårdh announced that she has decided to step down from the company's Board of Directors due to personal reasons.
Despite the global COVID-19 pandemic data collection for the POLAR phase III program is progressing according to plan with a data cut-off targeted for the third quarter 2020. We are grateful for the commitments of participating patients and investigating sites for this achievement. In these uncertain and unsettling times, our focus on Aladote and the ongoing regulatory interactions and clinical study remains firm. I look forward to relaying news to you around the planned study, as well as the data from the POLAR program.

Nicklas Westerholm, CEO
PledPharma AB, Stockholm