内容参考成果christer ilyapharma

1、Developing next-generation biological drugs for treating wounds in skin and mucosa22-28 May 2017 Christer Johansson Process Development christeraqps.se Ilya Pharma now invites experienced private investors, industrial partners and venture capitalist with know-how in drug development to join as new o

2、wners and finance activities associated with the planned Phase I clinical trial.Technology and MOAThe technology innovation: modified lactic acid bacteria (probiotics) act as small bioreactors to produce and deliver human effector proteins at the site of the woundPotential applications: to a body su

3、rface, e.g. skin, wounds, colon, the rest of the GI tract such as the mouth and nose, as well as the eyes and lungs. Business model: Licensing; technology platform or single drug candidates after cPoC.IP: PCT-application going, 1-2 new applications 2017. Business modelDeveloped by Ilya PharmaDevelop

4、ed in associated labsIBD inflammatory bowel diseaseEV100, EV101 and EV102 are lactic acid bacteria expressing three different human effector proteins targeting the functions of immune cells in the skin and in the gastrointestinal tract. Stable formulationIt worksIntended drug productRapid wound clos

5、ure in 24 hDFU segment 2011-2014 USbn.Wound care market 2014-2018 USbn.MarketThe wound-care market is now USD 14 bn with an expected growth of 6% p.a. until 2018. Treatment of chronic wounds eg Diabetic Foot Ulcers (DFU) 1,7 Bn USD 2014Wound-care includes all skin wounds, e.g. acute traumatic wounds

6、, burn wounds, post-surgical wounds as well as chronic wounds. The candidate drug EV100 66% reduction of wound surface area during the first 24 hours compared to only 33% in the control group. LBEV100Reepithelialisation in human skin biopsiesWound healing in miceEV100LBNo treatmentMechanismOur techn

7、ology allows for continuous delivery of human effector proteins for one hour in wounds (the Lactobacillus dies after some hours due to exhaustion). This is what actually happens: treatment with EV100 changes the microenvironment and the body thinks that the wound is much larger than it actually is.

8、Its cells react accordingly and prioritize the healing. The protein expressed by the lactic acid bacteria targets the function of immune cells involved in the healing process. macrophages in the bottom of the wound multiply, change their phenotype, and produce more TGF-beta, which drives the healing

9、 process. EV100A. The innovation; genetically-modified lactic acid bacteria and the drug substance. B. Freeze-dried cake of our genetically-modified lactic acid bacteria in a glass vial. C. Draft design of the intended final product, a two-compartment syringe with one solid phase with freeze-dried b

10、acteria and one liquid phase with the water equivalent. The drug product is called IlyaT100 2. Mixing compartments immediately revives the freezedried bacteria.3. Five minutes after mixing, the solution is applied directly to the wound surface. Living probiotic bacteria only adhere to the wound surf

11、ace where they produce and secrete the human effector protein for one hour. Immune cells in the wound are affected by the expressed protein and start to drive the healing process. 1. Prepare the wound, remove dead tissue and clean the wound surface.Drug developmentWe are currently at step B. The for

12、mulation has a maintained effect on wound healing and good stability at +4C. Positioning and competitionPositioning and competitionCharacteristics of our proposed treatment, EV100: *Accelerates wound-healing with an efficiency never before reported (!) in preclinical models. *Bacteria can be freeze-

13、dried with maintained effect using a simple and scalable GMP-protocol. *Very cost-efficient system for delivering biological drugs compared to recombinant proteins. *The lactic acid produced has an antibiotic effect on wound-pathogenic bacteria. Execution plan to Phase I clinical dataActivityWhenHow

14、/whoCost (k)Financed howCellbankFeb 2017Verified in-house, performed by CRO (Medicago)15GrantSafety studies GMO LactobacillusDec 2016-March 2017In-house50GrantProduction process scale-up, 13 lMarch 2017Protocols prepared in-house, performed by CRO (Medicago)50GrantPharmacokinetics (PK) studyMarch 20

15、17In-house15GrantScientific advice, construction and tox protocol.April-May 2017Prepared in-house and with regulatory experts20GrantApplication to use GMOApril-May 2017Prepared in-house and with regulatory experts10Issue 1Take PCT to national phase and new IPMay 2017In-house and Dehns200Issue 1Repea

16、ted dose tox in mini-pigs*May 2017CRO (CitoxLabs)300Issue 1GMP-production, 500 lMay-July 2017GMO (Biovian or Fraunhofer Institute)1200Issue 2Scientific advice, clinical programAugust-October 2017Prepared in-house and with regulatory and clinical experts20Issue 2Completion of IND-fileAugust-December

17、2017Prepared in-house and with regulatory and clinical experts and CRO (CTC). Additional experiments for CMC in-house and CRO, (AmatsiSEPS).200Issue 2Submission for ethical approvalOctober 2017Prepared in-house and with regulatory and clinical experts and CRO (CTC).20Issue 2Phase I clinical trialDec

18、ember 2017-February 2018At Uppsala University Hospital, headed by Fredrik Huss and run by CTC. 24 healthy volunteers, 8-10 punch biopsy wounds induced/person, 4 weeks.720Issue 3* If things proceed as planned with the scale-up production process, we can use the material in the tox studies. If not, th

19、e GMP-production has to come before the repeated dose tox.In addition, we are continuously seeking opportunities in public funding such as national and EU-grants. Any grants would be a positive contribution, but we cannot at this moment rely on grants. 3 MIssue 1 510k Issue 2 1440kIssue 3 720kClinic

20、al valueClinical valueWounds, both acute and chronic, entail huge distress for both patients and caregivers alike. Small wounds becoming chronic are particularly problematic for people with diabetes and/or reduced peripheral perfusion, as these conditions are associated with impaired wound healing.

21、Kick-starting and accelerating the healing of chronic skin wounds in persons with Type 2 diabetes is the first intended indication for the proposed lead drug candidate. This indication is commonly called diabetic foot ulcers or DFUs. Other types of wounds are also expected to benefit from treatment

22、with the proposed drug.Ilya Pharma has a competitive clinical strategy to treat chronic wounds. The strategy can be shared in detail in later discussions and all options fit with the outlined protocol for the proposed Phase I clinical study. Effects of accelerated healing time of chronic foot ulcers

23、 in patients with diabetes.Regulatory environmentRegulatory environmentNext-generation biological drugs living organisms Our lead candidate is classified as an advanced therapy medicinal product (ATMP), a living organism drug, by the EMA in 2016. This implies both opportunity and risk. There are regulatory challenges using living organisms as vectors for the local production and delivery of biological drugs. Two larger analyses of guidelines applying to ATMPs and the path forward for our lead candidate have been performed. The regulatory