Interim report January-March 2020

January-March
·         Quarterly net sales MSEK 11,7 (54.9)
·         Quarterly result MSEK till -42,8 (22,9)
·         Cash and cash equivalents MSEK 221,1 (258,0)
·         Cash flow from operating activities MSEK -37.2 (27.0)
·         Result per share SEK -0.8 (0.5)

PledOx®
·         US Food and Drug and Administration (FDA) and French regulatory authority (ANSM) issued a clinical hold in the US and France, respectively, of the phase III POLAR studies
·         PledPharma places dosing of patients in the POLAR program on hold


Aladote®
·         PledPharma has following interactions with the FDA and the European Medicines Agency (EMA) finalised the development program for Aladote. The development program consists of one pivotal Phase II/III study which is expected to be sufficient for a marketing authorisation application in both US and EU.
 
Significant events after the reporting period
PledPharma to close the POLAR phase 3 program with a data cut-off targeted for the third quarter 2020. Data generated will enable a thorough evaluation of safety and efficacy to determine the future of PledOx

Comments from the CEO

PledOx POLAR program
In the first quarter of this year, PledPharma experienced a major setback with the pivotal clinical POLAR program for the 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. In January, the US FDA issued a clinical hold in the US on the POLAR program due to a less than a handful of observed CNS-related adverse events.
In early March, the French regulatory authority ANSM expressed the same concern as the FDA on less than a handful of observed CNS adverse events and requested that recruitment and dosing of patients should stop in France. PledPharma maintains its position that these CNS-related events are not related to PledOx; a position which is also supported by the independent Drug Safety Monitoring Board (DSMB) and an additional independent external evaluation of these cases.

POLAR program data cut-off in Q3 2020
In April, we took the decision to close the POLAR program, with a data cut-off targeted for the third quarter 2020 and a thorough evaluation of the safety and efficacy will follow to determine the future of PledOx. The decision was taken after a recommendation from DSMB to stop the studies due to severe allergic reactions in eight patients, which have been observed after repeated dosing. Allergic hypersensitivity reactions are not uncommon in relation to platinum-based chemotherapy. However, the DSMB recommendation implies that there is an increased risk in subjects treated with PledOx. We are currently working to better understand why these allergic hypersensitivity reactions occur withcoadministration of oxaliplatin and why they occur after repeated dosing.
The current status of the POLAR program is as follows:
A total of 590 patients out of the planned 700 patients have been randomized. In terms of dosing, 420 patients have completed more than 6 cycles of treatment with study drug and about 250 more than 9 cycles. We expect that these patients randomized to PledOx have received sufficient treatment to evaluate prevention of neuropathy.
 
Our assessment is that the totality of data generated will enable a thorough efficacy and safety evaluation 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.
The safety of patients in our clinical studies is our most important responsibility. We will now concentrate on collecting the remaining data in the challenging COVID-19 environment and how we can best use the data from the POLAR studies to potentially support future clinical trials, as we believe nerve damage associated with chemotherapy remains an unmet medical need.

Continued development of Aladote
Our focus on this important asset Aladote and the forthcoming regulatory interactions and clinical study remain 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 administrationin the clinical trials with calmangafodipir.
In order to continue the development of our clinical portfolio, we are well financed with approximately 221 million SEK in cash and cash equivalents reported at the end of the first quarter 2020.
The Covid-19 pandemic will most likely have far-reaching financial and structural consequences, not the least within the life science sector, where many clinical trials are now forced to be put on hold due to the acute situation at hospitals and potential study centres. Despite these uncertain and unsettling times, our focus on Aladote and the forthcoming 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