Kiadis Pharma
Written by
Kiadis Pharma |
One-year follow-up data presented at ASH |
Clinical data update |
Pharma & biotech |
8 December 2016 |
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Kiadis Pharma has presented one-year follow-up data from a Phase II study in leukaemia patients (n=23) at the 58th meeting of the American Society of Hematology (ASH) in San Diego, US. Patients were administered ATIR101 after a haematopoietic stem cell transplant (HSCT) from a partially matching donor. The primary endpoint of transplant-related mortality (TRM) and secondary endpoint overall survival (OS) for patients receiving HSCT+ATIR101 were significantly higher than patients receiving HSCT alone from an observational control group. We are encouraged to see the low incidence of relapse in the ATIR101 arm in this high-risk patient population. Our valuation is €383.2m or €27.4 per share.
Year |
Revenue |
PBT* |
EPS* |
DPS |
P/E |
Yield |
12/14 |
0.00 |
(7.21) |
(0.07) |
0.0 |
N/A |
N/A |
12/15 |
0.00 |
(17.35) |
(0.14) |
0.0 |
N/A |
N/A |
12/16e |
0.00 |
(9.99) |
(0.07) |
0.0 |
N/A |
N/A |
12/17e |
0.00 |
(13.48) |
(0.10) |
0.0 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding intangible amortisation, exceptional items and share-based payments.
ATIR101: Increasingly positive data at one year
In this open-label single dose Phase II study, ATIR101 administered after HSCT showed a significant reduction in the primary endpoint of TRM at 32% vs 70% for HSCT only (p=0.007) of a historical comparator group. Overall survival was 61% for HSCT+ATIR101 vs 20% for HSCT only (p=0.0023). There were no cases of grade III-IV acute Graft vs Host Disease (GVHD), only three cases of grade II acute GVHD, and one chronic GVHD. Thus, event-free survival rate (GRFS) was 57% after one year, which is higher than 20% for the historic group, even for matching unrelated donors (41%) and post-transplant cyclophosphamide (PTCy) of 33% as reported by Solh et al. (2016).
Up next: Start Phase III trial and EU filing
Kiadis plans to initiate a Phase III trial in patients with acute leukaemia soon after regulatory approval of the protocol (we assume Q117). Patients will be randomised to receive a single dose of ATIR101 or PTCy after haploidentical HSCT. Furthermore, on the back of the Phase II data, the company plans to submit a Marketing Authorization Application for conditional approval to the European Medicines Agency (EMA) in Q117. ATIR201 will start clinical testing in thalassemia in H216.
Valuation: Upgraded to €383.2m from €327.3m
We are slightly increasing the probability of success for ATIR101 in the EU from 70% to 75% to reflect our positive stance on Kiadis receiving EMA approval based on positive Phase II data and the precedent of MolMed, which received conditional approval on lower one-year survival data of 49%. We are also rolling the valuation forward in time. This results in an increased rNPV valuation of €383.2m vs previous €327.3m.
One-year Phase II data confirms efficacy of ATIR101
Kiadis Pharma has presented one-year data of its ongoing Phase II trial in patients with acute leukaemia subject to HSCT at the 58th meeting of the ASH. This is a multicentre, open-label Phase II trial (NCT01794299, CR-AIR-007) evaluating the safety and efficacy of a T-cell depleted haploidentical transplant followed by ATIR101 infusion at a median of 28 days post-transplant. The primary endpoint is TRM; relevant secondary endpoints are OS and progression-free survival. The trial included 23 patients (16 with acute myeloid leukaemia and seven with acute lymphoblastic leukaemia) who were in first or second remission. Most patients (57%) had a high or very high risk of leukaemia; the rest had an intermediate risk. Patients did not receive post-transplant GVHD prophylaxis.
There was no TRM after 100 days of treatment. There were seven deaths in the ATIR101 arm as a result of TRM at one year post-HSCT, resulting in a TRM rate of 32%. All seven patients died from infection. In addition, two patients died from disease relapse, resulting in an overall survival of 61%. There were no cases of grade III-IV acute GVHD and only three of grade II acute GVHD. One patient had chronic GVHD.
Exhibit 1: Phase II clinical data at one-year follow up
Endpoint |
HSCT+ ATIR101 |
HSCT only |
|
TRM |
32% |
70% |
|
OS |
61% |
20% |
|
GFRS |
57% |
20% |
|
Grade III/IV acute GVHD |
0% |
N.D. |
|
Grade II acute GVHD |
13% |
N.D. |
|
Chronic GVHD |
4.3% |
N.D. |
|
Source: Edison Investment Research, Kiadis Pharma. Note: N.D. = not disclosed.
These data compare favourably with a historic control group obtained from the same centres and with the same inclusion/exclusion criteria that had undergone a transplant from haploidentical family members (NCT02188290/CR-AIR-006). When compared to the control group (n=35), TRM was significantly lower in patients given ATIR101 after a T-cell depleted haplo HSCT with a one-year TRM of 32% versus 70% for HSCT only (p=0.007). Overall survival was significantly higher in the HSCT+ATIR101 group (61%), compared to HSCT alone (p=0.0023).
Event-free survival, defined as GVHD-free, relapse-free survival (GRFS1), was 57% after one year in the HSCT+ATIR101 group, which is higher than 20% for the HSCT-only group. Interestingly, this result is also higher than matching unrelated donors (41%) in the same group. According to Sol(h et al. (2016), patients receiving cyclophosphamide after haploidentical HSCT had a GFRS of 33%.
It is a composite endpoint that measures survival free of morbidity defined as grade III-IV aGVHD, cGVHD requiring systemic treatment, cancer relapse, or death.
EU registration and Phase III plans on track
We expect the full Phase III trial to start in Q117. The protocol has been submitted to regulatory authorities in the EU and US and is currently under review for approval. Patients will receive either ATIR101 or the Baltimore approach (PTCy) after haploidentical HSCT. The primary endpoint of the Phase III trial will be GFRS. Moreover, Kiadis anticipates an EU regulatory filing in Q117 on the back of the Phase II results. Additionally, ATIR101 is undergoing a Phase II study in which a second dose of the product is administered to patients before the 100-day period post-transplantation to support faster immune-reconstitution. The full enrolment and safety readout will be completed in H217.
The second product, ATIR201 for thalassemia, is currently in a preclinical stage. A Phase I/II programme is slated to start H217. The development pipeline is summarised in Exhibit 2.
Exhibit 2: Kiadis Pharma product portfolio
Product |
Indication |
Status |
Potential launch |
Comments |
ATIR101 |
Leukaemia |
Phase II |
2018 |
Presented positive data at six months and one year. Regulatory filing in EU in Q117. Phase III start in Q117. |
ATIR201 |
Thalassemia |
Preclinical |
2022 |
Preclinical stage. Start Phase I/II trial in H216. |
Source: Edison Investment Research, Kiadis Pharma