Tonix Pharmaceuticals Holding Corp. 8-K

 

Exhibit 99.02

 

 

Monotherapy with TNX - 1500, an Fc - modified anti - CD154 mAb , prolongs cardiac allograft survival in cynomolgus monkeys Kohei Kinoshita 1 , Shuhei Miura 1 , Zahra Habibabady 1 ,Madelyn Ma 1 , Gannon McGrath 1 , Ryan Chaban 1 , Siobhan Fogarty 2 , Patrick Maguire 2 , Bruce Daugherty 2 , Seth Lederman 2 , Richard N. Pierson III 1 1 Center for Transplantation Sciences, Massachusetts General Hospital, Boston MA, 2 Tonix Pharmaceuticals, Chatham, NJ, USA

   
 

Kohei Kinoshita , MD, Research fellow Center for Transplantation Sciences, Massachusetts General Hospital, Boston MA I have no financial relationships with commercial interests to disclose AND SF, BD and SL are Tonix employees, and PM is a Tonix consultant This work was supported by Tonix through a Sponsored Research Agreement.

   
 

Emerging Costimulation Blockade: aCD154 Zhang et al. Immunotherapy 2015 MHC + Ag TCR B7 - 1 CTLA - 4 B7 - 2 CD28 CD40 CD154 APC T cell

   
 

 1 st generation a nti - CD154 mAb prolonged graft survival in NHP Tx model( Hrt /Kid /islet/skin )  Major thrombotic events in the clinical trial ∵ Activate platelets via Fc γ RIIa express CD154 m Ab form immune complexes with soluble - CA154 and them  3 rd generation Fc - mod aCD154 mAb hu5c8 hu5c8 TNX - 1500* hu5c8 Full Fab Fc γ RIIa - modulated Fc region Mutated Fc γ RIIa - binding region FcRn - binding region *TNX - 1500 is an investigational new biologic and has not been approved for any indication RK0

   
 

0 3 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112 119 126 133 147 154 161 168 175 140 1 80 S tandard - dose TNX - 1500 m onoRx (sTNX, n=5) 30 mg/kg Twice weekly 20 mg/kg W eekly MMF 200 mg PO daily Low - dose TNX - 1500 + MMF (loTNX - 1500 + MMF, n=4) 10 mg/kg Weekly 30 mg/kg Twice weekly 20 mg/kg Monthly Low - dose TNX - 1500 m onoRx (loTNX - 1500, n=4) 10 mg/kg Weekly 30 mg/kg Twice weekly 20 mg/kg Monthly Primatized Hu5c8 monoRx (Reference, n=5) 10 mg/kg Weekly 30 mg/kg Twice weekly 20 mg/kg Monthly Methods - Heterotopic abdominal heart allotransplant model Protocol biopsies: POD ~45 and 90 EOS: POD 180

   
 

hu5c8 (n=4) (Rx off d90) loTNX (n=4) loTNX + MMF (n=4) stTNX (n=5) (Rx off d175) MST (range) 133 days (90 - 173) 99 days (35 - 183) 88 days (58 - 146) >265 days (116 - 305) P<0.05 for all comparisons against stTNX Rejection after cessation of all IS treatment Explant of beating graft EOS Results - Heart Allograft Survival in NHPs is significantly prolonged with Standard dose TNX - 1500 ( stTNX )

   
 

Results - Platelet counts were stable and No thromboembolic complications were observed

   
 

(defined as CD4 + CD25 + CD127loFoxp3 + ) Ratio of T eff /T reg Results - stTNX suppressed the rise in Teff/Tregs ratio at the final time - point more effectively than loTNX+MMF

   
 

CAV; Cardiac Allograft Vasculopathy ISHLT; International Society for Heart and Lung Tx ISHLT scores CAV severity scores Results - CAV significantly more severe with loTNX - 1500+MMF * P<0.05 ** P<0.01 *** P<0.005 **** p<0.001

   
 

Positive 1/4 animals Positive 2/4 animals Positive 0/5 animals Positive 0/5 animals Positive 0/5 animals Positive 0/5 animals Positive 0/4 animals Positive 0/4 animals Positive 1/4 animals IgM IgG loTNX (n=4) loTNX+MMF (n=4) sTNX (n=5) Positive 2/4 animals Positive 2/4 animals Positive 0/4 animals CD3 + CD20 - T cells (MHC Class1) CD3 - CD20 + B cells (MHC Class1 and Class2) IgG IgM Relative to Baseline Postoperative day Results - TNX - 1500 suppresses anti - donor - alloantibody elaboration

   
 

Conclusions  Standard - dose TNX - 1500 inhibits pathologic alloimmunity in NHPs • Consistently prolonged NHP heart allograft survival • No clinical thrombotic events • Relative expansion of Tregs in peripheral blood • No CMV activation (no prophylaxis)  MMF does not improve heart results with low - dose TNX - 1500 • Does MMF interfere with Treg expansion, function under aCD154 Rx?  TNX - 1500 inhibits alloantibody elaboration, class switching • Dose - dependent effect (Kirk AD et al) Thank you for your listening!