Quarterly Report I 19/20

September 2019 – November 2019, Diamyd Medical AB (publ), Fiscal year 2019/2020
 

Developing therapies for type 1 diabetes
Diamyd Medical’s B-share is traded on Nasdaq First North Growth Market under the ticker DMYD B.
Further information is available on https://www.diamyd.com

Figures in parentheses relate to the corresponding period previous financial year.

September 1, 2019 – November 30, 2019

• Net income: MSEK 0.1 (0.3)
• Net result: MSEK -6.8 (-8.5)
• Result per share: SEK -0.1 (-0.2)
• Cash flow from operating activities: MSEK -6.1 (-10.8)
• Liquid assets and short-term investments as of November 30, 2019:    MSEK 50.6 (31.8)

Significant events first quarter, September– November

• ReGenerate-1: Positive safety review of Remygen® gave clearance to start next part of Phase I/II trial in type 1 diabetes patients
• Manufacturing process may be moved to a new manufacturer
• Agreement for intralymphatic Diamyd® trial in LADA patients
• Preliminary results were presented from a GABA/Diamyd® trial
• DIAGNODE-2: Patients will be offered longer participation in the European Phase IIb trial with the diabetes vaccine Diamyd®    
• DIAGNODE-2: Feasibility study supported the use of intralymphatic injections of Diamyd®

Significant events after the reporting period

• DIAGNODE-1: Positive Top-line results from Phase I/II trial with intralymphatic Diamyd®
• ReGenerate-1: The main part of the Phase I/II trial with Remygen® in type 1 diabetes started
• Significant effect of Diamyd® in Type 1 diabetes shown in comprehensive analysis of previous phase III and phase II trials

Comments by CEO Ulf Hannelius
I am proud to say that the first quarter of the financial year 2019/2020 has substantially strengthened Diamyd Medical as a company. Recent clinical results and analyses provide strong support for the efficacy of the diabetes vaccine Diamyd® and significantly decreases the risk in the clinical development program for our type 1 diabetes therapy.

In December, we announced results from a comprehensive analysis based on more than 530 type 1 diabetes patients who participated in three previous placebo controlled randomized trials with Diamyd®. The analysis, a collaborative effort between Diamyd Medical, academic researchers and clinicians, is based on the hypothesis that the efficacy of the Diamyd®-therapy differs depending on the presence or absence of certain genes. These genes code for the HLA molecule that in turn determines how antigens are recognized and presented by the immune system. The field has long known that genetic variations in the HLA molecule constitute one of the most significant risk factors for type 1 diabetes and other autoimmune diseases. Only in recent years has this led to the realization that these genes may also be central to defining different subgroups of patients in order to tailor treatments based on the patient's underlying disease mechanism, so-called precision medicine.

Against this background, it is of the utmost interest that the results indeed show that the effect of Diamyd® is influenced by the patient’s HLA genes. About 50% of all patients included in the analysis have HLA genes that associate with the best effect of the vaccine. More specifically, the highest doses (3 or 4 subcutaneous injections) of Diamyd® in this subgroup of patients, give a statistically significant treatment effect. Patients that received a higher dose of Diamyd® are estimated to have on average up to 60% more insulin producing capacity compared to placebo at 15 months from baseline.

These results give us the opportunity to precisely identify the patients that have a high likelihood of responding to Diamyd®. Moreover, they also provide answers to questions that were raised following the phase III trial which did not meet its primary end point in 2011. A previous large-scale analysis (published in the beginning of 2017) showed that Diamyd® with a very high probability has a positive but limited (approximately 16-20%) biological effect on preserving the insulin producing capacity compared to placebo. The new analysis focusing on specific subgroups shows that the effect is both positive AND clinically relevant when targeting the right patient group. Furthermore, it is encouraging that additional doses of Diamyd® lead to better efficacy. This ties very nicely to our Diamyd®-program; the recently announced topline results from DIAGNODE-1 and the European DIAGNODE-2 trial with three intralymphatic injections of Diamyd®, where we expect to present results the third quarter later this year.

The topline results from DIAGNODE-1, also presented in December, showed that the patients had well controlled blood glucose levels and used less insulin than expected. What is perhaps even more exiting is that a fourth booster injection, given to three patients 30 months after baseline, preserved the insulin producing capacity for a whole year. This shows that additional doses of Diamyd® administered into the lymph node seem to lead to improved efficacy and goes well with the dose-response relationship seen in the comprehensive analysis mentioned above.

The new insights into Diamyd® in type 1 diabetes treatment are significant and we benefit from them in all aspects of our work including defining the analysis plan for DIAGNODE-2, planning for the upcoming phase III program and in our discussions with potential partners. We have a very interesting and intense period ahead of us.

Stockholm, January 22, 2020
Ulf Hannelius, President and CEO
Two drugs in clinical development

Diamyd® and Remygen® are drugs in clinical development that focus on the underlying disease mechanisms of diabetes; the dysfunction and loss of insulin-producing beta cells in the pancreas.                         

Diamyd® is an antigen-specific immunotherapy for the treatment of autoimmune diabetes (type 1 diabetes).

Clinical data indicate the potential of the diabetes vaccine Diamyd® to halt or stop the autoimmune destruction of insulin-producing beta cells. The effect is achieved by antigen-specific reprogramming of immune cells by administration of low doses of Diamyd® in superficial lymph nodes.

By maintaining the endogenous insulin production, Diamyd® has the potential to make a significant difference in the daily life of patients as well significantly reduce the complications of type 1 diabetes.

Intralymphatic treatment with Diamyd® is now being investigated in a clinical Phase IIb trial (DIAGNODE-2), with the aim of confirming the previously demonstrated clinical effect from a pilot trial in type 1 diabetes patients (DIAGNODE-1).

Remygen® is an oral regenerative and immunomodulatory therapy for the treatment of autoimmune- and type 2 diabetes.

By stimulating the growth of insulin-producing cells, Remygen® has the potential to reverse the disease progression in autoimmune- and type 2 diabetes.

Remygen® is now being investigated in a clinical Phase I/II trial (ReGenerate-1), where clinical efficacy is evaluated with the aim of optimizing treatment ahead of registration-based trials.

Significant events during the first quarter

September 1, 2019 – November 30, 2019

Positive safety review of Remygen® gave clearance to start next part of Phase I/II trial in type 1 diabetes patients
The initial safety and dose escalation part of the Phase I/II trial with Remygen® in type 1 diabetes patients, ReGenerate-1, was completed. The safety data from the six patients included in the first part of the trial was evaluated by an independent Data Safety Monitoring Board (DSMB) who recommended that the main study could start.

Manufacturing process may be moved to a new manufacturer
Diamyd Medical’s manufacturing process of rhGAD65, the active ingredient in the diabetes vaccine Diamyd®, may be moved to a new manufacturer. Protein Sciences has offered to support Diamyd Medical in a transition of the current process to a new manufacturer, the details of which will need to be discussed and agreed on by the parties.

Diamyd Medical entered agreement for intralymphatic Diamyd® trial in LADA patients
The agreement with the Norwegian University of Science and Technology in Trondheim (NTNU) refers to a first, investigator initiated clinical Phase II trial with the diabetes vaccine Diamyd® administered directly into the lymph node in a limited number of patients newly diagnosed with LADA (Latent Autoimmune Diabetes in Adults).

Preliminary results were presented from a GABA/Diamyd® trial
Preliminary results from the US investigator initiated GABA/Diamyd® trial were presented by Professor Kenneth McCormick at University of Alabama at Birmingham, Principal Investigator and Sponsor of the trial, at the annual meeting of the EASD. Initial analyses indicated that GABA alone or in combination with two 20 µg Diamyd® injections under the skin (in contrast to three injections into a lymph node as in the ongoing DIAGNODE trial) to recent onset type 1 diabetes patients does not significantly affected insulin production, blood glucose values or insulin dose compared to placebo. A potential positive effect of GABA on lowering glucagon levels was observed. No serious side effects were reported. In-depth metabolic analyses and immunological results are expected to follow.

Patients offered longer participation in the European Phase IIb trial with the diabetes vaccine Diamyd®
Patients participating in the diabetes trial DIAGNODE-2 who have not yet performed their last visit at 15 months, are offered to be included in a 9 month extension of the trial, which means that these patients will be followed for a total of 24 months. Top-line results of the trial will be presented after 15 months, in the third quarter of 2020. The purpose of the longer follow-up is to further strengthen the regulatory package with safety and efficacy data prior to a potential earlier market application.

Feasibility study supported the use of intralymphatic injections of Diamyd®
A feasibility study performed as a Master Thesis at Uppsala University and supervised by Diamyd Medical, supported the use of ultrasound guided intralymphatic injections for clinical routine use.

Significant events after the reporting period

Positive Top-line results from Phase I/II trial with intralymphatic Diamyd®
When all 12 patients had been followed throughout the 30-month period in the open-label trial DIAGNODE-1, the patients showed on average a positive clinical course with a near normal long-term blood sugar and a low need for externally supplied insulin. The three patients who received an extra Diamyd® injection into the lymph node after their 30-month visit showed a maintained own insulin production between the 30- and 43-month visits, as well as lower long-term blood sugar and insulin requirements compared to baseline. Safety looked good and no serious side effects had been reported.

The main part of the Phase I/II trial ReGenerate-1 with Remygen®   started
Four patients had already been included in the trial and additional patients were scheduled to be included in December and January. Compilation of metabolic results from the completed safety and dose escalation part of the trial awaits a final experimental analysis and is expected to be announced in early 2020.

Significant effect of Diamyd® in Type 1 diabetes shown in a comprehensive analysis of previous Phase III and Phase II trials
A new analysis based on data from more than 530 individual patients from previous Phase III and II trials in Europe and US with the diabetes vaccine Diamyd® identified genetically defined subgroups of type 1 diabetes patients that showed a positive and statistically significant dose-dependent treatment response.
 

Ongoing clinical trials
Type 1 diabetes is a devastating disease which requires daily treatment with insulin to sustain life. The importance of finding a drug that improves the prospects for patients with diabetes is of utmost importance. The effect of intralymphatic administration of Diamyd®, an antigen-specific immunotherapy aimed at stopping the immune system's attack on insulin-producing beta cells in autoimmune diabetes, is evaluated in the Phase IIb trial DIAGNODE-2. Remygen®, which aims to stimulate the growth of beta cells in patients with diabetes, is now evaluated in patients in a Phase I/II trial.

Trial with Diamyd® in lymph node

• DIAGNODE -2 – DIAMYD® IN LYMPH NODES WITH ORAL SUPPLEMENTATION OF VITAMIN D

A follow-up double-blind randomized clinical trial where Diamyd® is administered directly into a lymph node with oral supplements of vitamin D. The trial encompasses 109 patients from Sweden, the Czech Republic, Spain and the Netherlands, aged 12–24 years who have recently been diagnosed with type 1 diabetes and will continue for a total of 15 months. As of autumn 2019, those patients who have not performed their last visit at 15 months are invited to participate in a nine months extension of the trial. 15-month results are expected to be presented in the third quarter of 2020. The aim of the trial is to evaluate the patients’ remaining insulin producing capacity. Coordinating Investigator is Professor Johnny Ludvigsson at Linköping University, Sweden. Diamyd Medical is the Sponsor of the trial.

Trial with Remygen® (GABA)

• REGENERATE-1 – REMYGEN® /ALPRAZOLAM

An open-label, investigator initiated clinical trial with Remygen®. The trial includes approximately 36 patients aged 18-50 who have had type 1 diabetes for more than five years with low to non-existing insulin production. The primary aim of the trial is to in a smaller dose escalation section evaluate the safety of Remygen®. The main trial also evaluates whether the insulin-producing cells can be regenerated using Remygen®, and in the combination of Remygen® and Alprazolam. The trial is led by Professor Per-Ola Carlsson at Uppsala University, Sponsor of the trial.

Other ongoing trial with Diamyd®

• DiAPREV-IT 2 – COMBINING DIAMYD® WITH VITAMIN D

A placebo-controlled investigator-initiated clinical trial, where Diamyd® is given subcutaneously and being tested in combination with vitamin D in children at high risk of developing type 1 diabetes, meaning that they have been found to have an ongoing autoimmune process but do not yet have any clinical symptoms of diabetes. The trial includes 26 children and results are expected in the beginning of 2020. The aim of the trial is to evaluate whether Diamyd® can delay or prevent the participants from presenting with type 1 diabetes. The trial is led by Dr. Helena Elding Larsson at Lund University, Sweden, Sponsor of the trial.

About Diamyd Medical
Diamyd Medical develops therapies for type 1 diabetes. The diabetes vaccine Diamyd® is an antigen-specific immunotherapy for the preservation of endogenous insulin production. Diamyd® has demonstrated good safety in trials encompassing more than 1,000 patients as well as significant effect in some pre-specified subgroups. Results from the Company’s European Phase IIb trial DIAGNODE-2, where the diabetes vaccine is administered directly into a lymph node in children and young adults with newly diagnosed type 1 diabetes, are expected to be presented in the third quarter of 2020. Diamyd Medical also develops the GABA-based investigational drug Remygen® for regeneration of endogenous insulin production. An investigator-initiated Remygen® trial in patients living with type 1 diabetes for more than five years is ongoing at Uppsala University Hospital. Diamyd Medical is one of the major shareholders in the stem cell company NextCell Pharma AB and has holdings in the medtech company Companion Medical, Inc., San Diego, USA.

Diamyd Medical’s B-share is traded on Nasdaq First North Growth Market under the ticker DMYD B. FNCA Sweden AB is the Company’s Certified Adviser; phone: +46 8-528 00 399, e-mail: info@fnca.se. Further information is available on https://www.diamyd.com.
 

*** The above is an excerpt from the report. To read the complete report, please visit https://www.diamyd.com, or see attached PDF ***

For more information, please contact:
Ulf Hannelius, President and CEO, phone: +46 736 35 42 41
Diamyd Medical AB (publ), Kungsgatan 29, SE-111 56 Stockholm, Sweden
Phone: +46 8 661 00 26 Fax: +46 8 661 63 68 E-mail: info@diamyd.com Reg. no: 556242-3797

The information was submitted for publication, through the agency of the contact person set out above, at 08.15 CET on January 22, 2020.

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