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our August operational update we outlined the trial designs and timelines for our two clinical programs, AIPAC and TACTI-mel, both of which are progressing on schedule. Data read out from the open-label, safety run-in cohorts of both trials is
expected by the end of the current quarter. We have recently filed a protocol amendment for the TACTI-mel trial to include patients that have brain metastases. We had previously excluded such patients, pending the generation of the initial safety
data on the first six patients in the trial. We are pleased to be able to offer these patients a chance to be treated with IMP321 in conjunction with their KEYTRUDA therapy. The operational update also highlighted that the Company s cash
reach has extended well into the fourth quarter of 2017 due to a rigorous focus on cost management. In our recent Annual Report to shareholders we also provided a comprehensive review of key activities for the financial year ended 30 June 2016. In
this investor update therefore, we have focused on what is transpiring in the broader biotech market with respect to immuno-oncology and the current trials targeting LAG-3. In this investor update we feature the vital work our laboratory staff in
Paris are undertaking to support our clinical studies, and introduce our Director of Clinical Development, Mr Christian Mueller. Lastly, we provide an overview of an innovative investigator initiated study called INSIGHT on which we are
collaborating with Professor Doctor Al-Batran, which will explore the potential for IMP321 as an activator of dendritic cells found within solid cancer tumours in new settings. Immuno-oncology Landscape Immuno-oncology (I-O) remains one of the
hottest areas in our industry, with recent market reports predicting peak global sales of $34Bn by 20241. Immunotherapy is a collective term given to treatments including vaccines and antibodies to treat cancers and infectious disease. I-O is the
use of specific types of immune therapies to treat cancer by controlling a patient s immune responses. Recently, one of our partners, Novartis, announced its decision to intensify its focus on I-O and move away from cell and gene therapies.
Novartis has announced multiple collaborations in various I-O combinations throughout this year. The current market leader, however, is Bristol Myers Squibb which dominates the I-O market with an impressive 10 different products targeting different
immune checkpoints. One of these checkpoints is LAG-3. In 2015, the value of deals done in the I-O space exceeded US$10.8Bn2. The growing level of industry interest in this space has continued in 2016 as illustrated by the table below of recent
acquisitions in the past few months of I-O assets. There have also been numerous collaborations for combination approaches announced. [Continued on p. 2] >> In this issue: Message from the CEO Immuno-oncology Landscape Insights into
INSIGHT Immune Monitoring in Paris Laboratory Q&A with Professor Doctor Salah-Eddin Al-Batran MD Prima Conference and Abstract Presentations Meet our Clinical Director Christian Mueller
[Continued from p. 1]
LAG-3 clinical development is gaining momentum with some of the world s largest pharmaceutical companies conducting trials of their version of an antibody that removes the
brakes from the immune system or that depletes the chronically LAG-3 activated T cells involved in auto-immunity (IMP731). Large pharma including Merck and Boehringer Ingelheim have recently announced they too are trialing their own versions of
LAG-3 antibodies. Coupled with our own IMP321 programs and the INSIGHT trial (which we discuss in more detail in this newsletter), the table below reproduced from a recent research report by Van Leeuwenhoeck Research (US) Inc shows how Prima is
either directly or indirectly involved in 5 of the 13 clinical trials currently targeting LAG-3.
Parties Value of deal
Novartis and Xencor: bispecific antibodies $150M upfront and $2.4Bn milestones
Flexus Biosciences $1.25Bn
Advaxis and Amgen collaboration $40M upfront and $25M investment plus $475M in milestones
Pfizer acquiring Medivation oncology portfolio $14Bn cash
Astellas acquiring Ganymed
422M upfront and 860M in milestones
Current Clinical Trials targeting LAG-33
Company Product Indication Phase Patients Remarks
Prima BioMed IMP321 Metastatic Breast Cancer
IIb 211 Adenocarcinoma Breast Stage IV. 2arms: Paclitaxel + IMP321 at the RPTD and Active Comparator: Comparator: Paclitaxel + Placebo
Metastatic Melanoma I 24 Multicentre, Open Label, Dose Escalation, Phase 1 Study in Patients
Novartis (partnership Prima) LAG525 Various Cancers I/II 416 May 9,
2015: Safety and Efficacy of LAG525 Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies
Bristol Myers Squibb BMS986016 Solid Tumors
I/IIa 360 Sep 25 2013: Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Mab Alone and in Comb with Anti-PD-1 Nivolumab, in Solid Tumors
Bristol Myers Squibb BMS986016 Hematologic Neo-plasms I/IIa 132 Feb 12, 2014: Phase 1/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy in
Combination With Anti-PD-1 Nivolumab, in Relapsed or Refract BCell Malignancies
Bristol Myers Squibb BMS986016 Glioblastoma I 68 2016_01_19: A Phase I Trial of
Anti-LAG-3 or Anti-CD137 Alone and in Combination With Anti-PD-1 in Patients With Recurrent GBM
Bristol Myers Squibb BMS986016 NSCLC II 504 April 21, 2016: A Phase
2, Fast Real Time Assessment of Combination Therapies in Immuno-Oncology Study in Subjects With Advanced NSCLC (FRACTION-Lung)
Merck MK4280 Solid Tumors I 70 March
22, 2016 : A Phase 1 Trial as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
GlaxoSmithKline (partnership Prima)
GSK2831781 Psoriasis I 67 July 17, 2014: A Randomised, Double Blind Placebo-Controlled, Single Asc Dose Study of Safety, Tolerability, Pharmacokinetics of a IV Dose in Healthy Subjects and Patients With Psoriasis
Tesaro TSR033 Various cancers Preclinical Antibodies to Human TIM3 and LAG3 Demonstrate Potent Activity in a Dendritic Cell / T Cell MLR and Have Increased Activity in Combination
Agenus/Incyte Macrogenics - MGD013 Undisclosed Various cancers Preclinical Preclinical At its 2015 R&D Day, pre-clinical data showing that the
co-blockade of PD-1 and LAG-3 via a PD-1 x LAG-3 DART molecule significantly enhanced T-cell response
Sanofi/Regeneron Cancer Preclinical
We still have a bit to learn about LAG-3, the role it plays and how we can target it to treat diseases like cancer. Even though Prima is still a small company, we occupy a
prominent position in the LAG-3 field and we are very pleased by the increasing awareness of this promising immune checkpoint.
3 Van Leeuwenhoeck Update Report: Prima BioMed at the
Forefront of LAG-3. September 1, 2016:
Insights into INSIGHT
announced to the market that we have entered into a collaborative study investigating the intra-tumoral injection of IMP321. This investigator sponsored study will be conducted by the Institute of Clinical Cancer Research (IKF), Krankenhaus Nordwest
GmbH in Frankfurt Germany.
Unfortunately, many solid tumours have evasive mechanisms to prevent the active killing of their cells. The tumour microen-vironment can
often contain a complex cocktail of immune system inhibitors generated by the tumour to switch off our normal mechanisms of controlling cancer.
explore the potential for IMP321 as an activator of local dendritic cells found within solid cancer tumours, as opposed to AIPAC that is looking at boosting all antigen presenting cell (APC) responses to solid tumours post chemotherapy, or TACTI-mel
where we aim to boost APC responses to help improve suboptimal responses to KEYTRUDA . Both AIPAC and TACTI-mel are directed at improving the respons es of circulating APC (dendritic cells and monocytes) while
INSIGHT will look to activate those APC s that are already directly infiltrating a tumour.
Lead Investigator of this pilot trial is Prof. Doctor Salah-Eddin Al-Batran, the Director of Oncology at the IKF. Prof. Doctor Al Batran is also featured in the
Q&A section of this investor update. Prima will provide the IMP321 clinical supply for the trial but there will be no material funding required from us. The commencement of the study is subject to all necessary regulatory and ethical allowances.
We believe this is an ideal opportunity to investigate further clinical applications for IMP321. Direct injection into tumours, if shown to be successful, could
much more rapidly activate a patients immune system to respond to their disease.
INSIGHT: An explorative, single center, open-labeled, phase I study to evaluate
the feasibility and safety of intra-tumoural, intra-peritoneal, and subcutaneous injections with IMP321 (LAG-3Ig fusion protein) for advanced stage solid tumor entities
Objectives Feasibility, safety and toxicity Immune response in whole blood and tumour tissue Identification of biomarkers that correlate with clinical response / clinical outcome
BMS acquired Flexus Biosciences Monocenter, open-labeled, phase I study
Planned Sample size Up to 40 patients
Clinical trial identifier: To be
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Immune Monitoring in Paris Laboratory
In addition to some research and development activities regarding LAG-3, staff at our laboratory in Ch tenay-Malabry, south of Paris, are kept busy
conducting immune monitoring for both our AIPAC and TACTI-mel clinical trials.
Patients in each of these trials are intensively monitored for their responses to
treatment with IMP321, including their immune response. Blood samples are collected at pre-specified intervals and shipped to Paris from different centers in Europe. The staff in the lab are experts in conducting specially designed assays that
are capable of analysing subtle changes in the immune status of patients. A separate vendor in Paris measures inflammatory cytokine levels and activation markers on blood samples. This is an essential activity to ensure the health and safety of our
patients but also for measuring and analysing the magnitude of responses to treatment with IMP321.
In parallel, for our TACTI-mel clinical trial in melanoma being
conducted in Australia, blood samples are collected and assessed at a local vendor in Melbourne by flow cytometry. These assays are evaluating the number of activated T cells and number of antigen presenting cells over the course of the treatment.
We then collectively analyse all of the data generated, together with the investigators at each of our clinical sites in order to have a more complete picture of
our patient responses.
Q&A with Professor Doctor Salah-Eddin Al-Batran MD
Q. What is an investigator sponsored study?
An investigator sponsored study
is typically an academic study planned and conducted by an investigator with expertise in his or her field to investigate a new therapeutic strategy or a new drug application, for example in a new indication. This can be prior to, or after market
authorisation. Companies producing the drug may provide material or support for the trial, but unlike clinical trials sponsored by biotech or pharmaceutical companies, they do not manage the trial or the data.
Investigator sponsored studies represent an important component of clinical research and drug development. They facilitate the exploration of innovative drugs in other indications
or within alternative combinations. They also help to cross-link high-end academic research with clinical drug development.
Q. Can you tell us a little about
I am Director of the Institute of Clinical Cancer Research and Director of GI Oncology at the Krankenhaus Nord-west-University Cancer Center, Frankfurt.
I am a qualified haematologist and oncologist and my main fields of interest are upper GI malignancies, specifically esophageal and stomach cancer. Approximately 10 years ago, I founded the FLOT Gastric Cancer Network, which comprises more than
180 medical centers.
Q. What are you hoping to achieve with the INSIGHT study?