ASLAN presented data at ASCO from a Phase Ib dosing study examining varlitinib in combination with carboplatin, paclitaxel and Herceptin. Patients were enrolled across a range of cancers, but the majority (20/37) were HER2+ metastatic breast cancer patients. The drug demonstrated efficacy across the study and the addition of Herceptin at the optimal dose did not induce toxicity, suggesting the potential of future combinations.
Written by
ASLAN Pharmaceuticals |
Additional clinical support for varlitinib |
Clinical update |
Pharma & biotech |
7 June 2018 |
Share price performance
Business description
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Analysts
ASLAN Pharmaceuticals is a research client of Edison Investment Research Limited |
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ASLAN presented data at ASCO from a Phase Ib dosing study examining varlitinib in combination with carboplatin, paclitaxel and Herceptin. Patients were enrolled across a range of cancers, but the majority (20/37) were HER2+ metastatic breast cancer patients. The drug demonstrated efficacy across the study and the addition of Herceptin at the optimal dose did not induce toxicity, suggesting the potential of future combinations.
Year end |
Revenue ($m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
12/16 |
11.5 |
(7.6) |
(0.07) |
0.0 |
N/A |
N/A |
12/17 |
0.0 |
(38.8) |
(0.31) |
0.0 |
N/A |
N/A |
12/18e |
0.0 |
(38.9) |
(0.25) |
0.0 |
N/A |
N/A |
12/19e |
0.7 |
(62.0) |
(0.35) |
0.0 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments. Note the functional currency of the company is US dollars.
Tolerable dose combination with Herceptin found
The study examined 37 patients with a median three prior therapies. It was structured as a dose de-escalation study, so the rate of dose-limiting toxicities were high by design, but largely in line with other chemotherapy combination regimens. These events included neutropenia and electrolyte disorders. Carboplatin combinations were not tolerated, but Herceptin had no effect in the arm in which it was tested.
More evidence of varlitinib efficacy
The evaluation of efficacy in this study is difficult given the advanced stage of these patients and the high degree of variability in the study protocol. However, a disease control rate (stable disease + partial response + complete response) of 81% in evaluable patients and 56% on an intent to treat basis was observed. Among the patients with HER2+ breast cancer, six were able to be controlled on single agent varlitinib for a median of seven months, which is comparable to the progression free survival seen with Herceptin + paclitaxel in the front line (7.1 months).
ASLAN uplists to NASDAQ
In May 2018, ASLAN completed an offering of 6m ADSs (each representing five ordinary shares) on NASDAQ at a price of $7.03. Proceeds were $42.2m gross/$36.8m net and an additional 0.9m ADSs will be offered in the underwriter’s greenshoe. We expect this to provide a runway through the major clinical catalysts of 2018 and 2019.
Valuation: Increased to $364m from $308m
We have increased our valuation to $364m (NT$11.0bn) from $308m (NT$9.3bn), although it is lower on a per-share basis: $11.04 per ADS (NT$66.68 per ordinary share) compared to $11.83 (NT$71.85) previously. We arrive at estimated net cash (Q118 + offering + greenshoe) of $70.2m. We expect the company to require $60m in additional capital to reach profitability in 2021.
New data presented at ASCO
The company presented two posters at the American Society of Clinical Oncology (ASCO) annual conference in June 2018. The first was a description of the company’s ongoing pivotal TREETOP study of varlitinib in biliary tract cancer (BTC), which did not provide any new clinical data. However, the company also presented data from an ongoing Phase Ib varlitinib combination dosing study. The trial is designed to examine varlitinib with and without Herceptin (trastuzumab, Roche) in combination with carboplatin and paclitaxel. The combination of Herceptin with a platinum drug and a dose of Taxol (such as carboplatin and paclitaxel respectively) is a common treatment for HER2+ breast cancer, which formed the majority of patients (20/37) in the study.
Interpreting the results of the study is complex given the multiple doses and four different active molecules being studied (Exhibit 1). The study was structured as a dose de-escalation, such that initial cohorts were at drug concentrations that were likely to cause dose limiting toxicities (DLTs). These DLTs included neutropenia (febrile and otherwise), as well as a number of electrolyte disorders (hypophosphatemia, hyponatremia and hypokalemia) among others. The latter are not uncommon in cancer patients undergoing chemotherapy, but are typically secondary to gastrological distress (vomiting, diarrhea, etc). Diarrhea (of any grade) was the most common adverse event (69%), followed by fatigue (67%). The study identified 300mg dosed twice a day, intermittently (four days on, three days off) in combination with paclitaxel as the optimal dose combination and that addition of Herceptin did not increase toxicity.
Exhibit 1: Safety results from Phase 1b dosing study
Varlitinib dosing |
Other drugs |
N |
DLT |
500mg BD cont. |
CP |
3 |
3 |
400mg BD cont. |
CP |
5 |
3 |
400mg BD int. |
CP |
4 |
2 |
300mg BD int. |
CP |
6 |
2 |
300mg BD int. |
P |
6 |
0 |
400mg BD int. |
P |
4 |
2 |
300mg BD cont. |
P |
6 |
4 |
300mg BD int. |
PT |
3 |
0 |
Source: ASCO abstracts. Notes: cont.=continuous dosing, int.=intermittent dosing, C=carboplatin, P=paclitaxel, T=trastuzumab, DLT=dose limiting toxicity, PR=partial response, SD=stable disease.
These data build on the previously available evidence that varlitinib is clinically active in a range of tumor types. 26 of the 37 patients were evaluable for efficacy of which there was one complete response (CR), nine partial response (PR) and eleven stable diseases (SD). The disease control rate (CR+PR+SD) across among these was 81%, and 57% on an intent to treat basis. Two partial responses and two stable diseases were seen at the optimal dose (out of six). For comparison, disease control using Herceptin and paclitaxel in the first line is 79%,1 so we find the results from this study to be a compelling response given the number of prior therapies in these patients (median three), and the general variability in the study protocol. The company also noted that of the 10 breast cancer patients that achieved disease control, six maintained it with varlitinib alone for a median of seven months. This is comparable to the progression-free survival seen with Herceptin and paclitaxel in the first line (7.1 months). Varlitinib was not found to be tolerable in the triple combination including carboplatin, which further improves PFS in the Herceptin combination (to 10.7 months), although we do not find this immediately limiting given the multiplicity of treatment options. However, it does speak to the differences between varlitinib and Herceptin, which is generally tolerable in this combination. The ability to combine varlitinib with Herceptin opens up a range of different potential treatment algorithms to be explored, although at this time more data are needed to draw any conclusions.
Robert N, et al. (2004) Randomized Phase III Study of Trastuzumab, Paclitaxel, and Carboplatin Compared With Trastuzumab and Paclitaxel in Women With HER-2–Overexpressing Metastatic Breast Cancer. J Clin. Onccol. 24, 2786-2792.
ASLAN uplists to NASDAQ
In March 2018, ASLAN announced the intent to uplist to the NASDAQ exchange, and subsequently in May priced an offering of ADSs: 6m ADSs (each representing five ordinary shares) at an offering price of $7.03, for proceeds of $42.2m gross/$36.8m net. An additional 0.9m ADSs will be offered in the underwriter’s greenshoe (and we have included this in our valuation, see Exhibit 3) . The proceeds will be used to support the ongoing clinical development of varlitinib, ASLAN003 and ASLAN004. The current financing should allow the company to progress through all its major clinical catalysts in 2018 and 2019.The company provided an updated timeline for these events, largely in line with our estimates (Exhibit 2).
Exhibit 2: Clinical catalyst timing
Drug |
Program |
Catalyst |
Timing |
Varlitinib |
Second-line BTC |
Pivotal top-line data |
2019 |
China pivotal top-line data |
Late 2018 |
||
First-line BTC |
Phase I/II data |
Late 2018 |
|
Gastric cancer |
Phase II top-line data |
H218 |
|
ASLAN003 |
AML |
Interim data |
H218 |
ASLAN004 |
Asthma |
IND |
Q318 |
Atopic dermatitis |
IND |
Q318 |
Source: ASLAN
Valuation
We have increased our valuation to $364m (NT$1.0bn) from $308m (NT$9.5bn), although it is lower on a per share basis: $11.04 per ADS (NT$66.68 per ordinary share) compared to $11.83 ($71.85) previously, as result of dilution from the recent NASDAQ IPO. The increase in the total valuation is driven by increased cash following the IPO (estimated $42m net including the greenshoe bringing total cash to $70m), as well as advancing our model to the most recent period.
Exhibit 3: Valuation of ASLAN
Program |
Indication |
Region |
Clinical stage |
Prob. of success |
Launch year |
Peak sales ($m) |
Margin/Royalties |
rNPV ($m) |
Varlitinib |
Second line BTC |
US + Europe |
Phase II/III |
30% |
2020 |
277 |
59% |
121.6 |
East Asia |
Phase II/III |
30% |
2019-2020 |
195 |
53-58% |
73.9 |
||
R&D |
-7.2 |
|||||||
First line GC |
US + Europe |
Phase II/III |
20% |
2021 |
182 |
57% |
31.8 |
|
East Asia |
Phase II/III |
20% |
2021 |
302 |
54-60% |
51.5 |
||
R&D |
-7.7 |
|||||||
Upfront and sales milestones payable |
-9.5 |
|||||||
ASLAN003 |
First line AML |
US + Europe |
Phase II ready |
10% |
2022 |
308 |
59% |
38.0 |
R&D |
-4.0 |
|||||||
ASLAN002 royalties |
First line BC + GC |
US + Europe |
Phase II |
15% |
2022 |
909 |
5% |
16.9 |
Unallocated costs |
-11.8 |
|||||||
Total |
293.4 |
|||||||
Net cash and equivalents (Q118+ IPO + greenshoe) ($m) |
70.2 |
|||||||
Total firm value ($m) |
363.7 |
|||||||
Total basic ADSs (m) |
32.9 |
|||||||
Value per ADS ($) |
11.04 |
|||||||
Source: ASLAN reports, Edison Investment Research
Financials
The company reported a loss of $8.6m (NT$255m) from Q118, of which $5.1m was attributable to R&D spending. We forecast R&D spending of $30.5m for the year, increasing to $34.3m in 2019 with the advancement of the ongoing clinical programs. The company recorded a $12m payment in the first quarter for the new license agreement with Array Pharma for varlitinib, and it will owe another $12m on the first anniversary. The company ended Q118 with $27.9m in cash. If we include expected net proceeds from the NASDAQ IPO including the greenshoe ($42.3m), we arrive at an estimated net cash of $70.2m. We expect the company to require additional capital in 2019 to finance the launch of varlitinib, which we record as $60m in illustrative debt (Exhibit 4).
Exhibit 4: Financial summary
$’000s |
2016 |
2017 |
2018e |
2019e |
||
31-December |
IFRS |
IFRS |
IFRS |
IFRS |
||
INCOME STATEMENT |
||||||
Revenue |
|
|
11,547 |
0 |
0 |
743 |
Cost of Sales |
(125) |
0 |
0 |
(111) |
||
Gross Profit |
11,422 |
0 |
0 |
631 |
||
R&D |
(13,165) |
(30,001) |
(30,526) |
(34,313) |
||
SG&A |
(6,956) |
(9,139) |
(10,966) |
(31,260) |
||
EBITDA |
|
|
(7,204) |
(37,803) |
(38,308) |
(61,613) |
Normalised operating profit |
|
|
(7,280) |
(38,013) |
(38,533) |
(61,837) |
Amortisation of acquired intangibles |
0 |
0 |
0 |
0 |
||
Exceptionals |
0 |
0 |
0 |
3 |
||
Share-based payments |
(1,420) |
(1,127) |
(2,959) |
(3,107) |
||
Reported operating profit |
(8,700) |
(39,140) |
(41,492) |
(64,941) |
||
Net Interest |
(477) |
(54) |
(198) |
(124) |
||
Joint ventures & associates (post tax) |
0 |
0 |
0 |
0 |
||
Exceptionals |
127 |
(699) |
(197) |
0 |
||
Profit Before Tax (norm) |
|
|
(7,629) |
(38,765) |
(38,929) |
(61,960) |
Profit Before Tax (reported) |
|
|
(9,049) |
(39,892) |
(41,888) |
(65,065) |
Reported tax |
0 |
0 |
0 |
0 |
||
Profit After Tax (norm) |
(7,629) |
(38,765) |
(38,929) |
(61,960) |
||
Profit After Tax (reported) |
(9,049) |
(39,892) |
(41,888) |
(65,065) |
||
Minority interests |
0 |
0 |
0 |
0 |
||
Discontinued operations |
0 |
0 |
0 |
0 |
||
Net income (normalised) |
(7,629) |
(38,765) |
(38,929) |
(61,960) |
||
Net income (reported) |
(9,049) |
(39,892) |
(41,888) |
(65,065) |
||
Basic average number of shares outstanding (m) |
105 |
124 |
157 |
175 |
||
EPS - basic normalised ($) |
|
|
(0.07) |
(0.31) |
(0.25) |
(0.35) |
EPS - diluted normalised ($) |
|
|
(0.07) |
(0.31) |
(0.25) |
(0.35) |
EPS - basic reported ($) |
|
|
(0.09) |
(0.32) |
(0.27) |
(0.37) |
Dividend ($) |
0.00 |
0.00 |
0.00 |
0.00 |
||
BALANCE SHEET |
||||||
Fixed Assets |
|
|
593 |
689 |
21,615 |
19,561 |
Intangible Assets |
84 |
84 |
21,053 |
18,999 |
||
Tangible Assets |
384 |
444 |
405 |
405 |
||
Investments & other |
125 |
161 |
158 |
158 |
||
Current Assets |
|
|
53,121 |
50,645 |
41,128 |
34,137 |
Stocks |
0 |
0 |
0 |
27 |
||
Debtors |
1,294 |
0 |
0 |
122 |
||
Cash & cash equivalents |
51,737 |
50,573 |
41,047 |
33,905 |
||
Other |
90 |
72 |
82 |
82 |
||
Current Liabilities |
|
|
(3,804) |
(5,979) |
(14,608) |
(7,078) |
Creditors |
(3,804) |
(5,979) |
(14,608) |
(7,078) |
||
Tax and social security |
0 |
0 |
0 |
0 |
||
Short term borrowings |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
||
Long Term Liabilities |
|
|
(8,336) |
(9,841) |
(10,524) |
(70,966) |
Long term borrowings |
(8,336) |
(9,679) |
(10,099) |
(70,541) |
||
Other long term liabilities |
0 |
(162) |
(425) |
(425) |
||
Net Assets |
|
|
41,575 |
35,513 |
37,611 |
(24,346) |
Minority interests |
0 |
0 |
0 |
0 |
||
Shareholders' equity |
|
|
41,575 |
35,513 |
37,611 |
(24,346) |
CASH FLOW |
||||||
Op Cash Flow before WC and tax |
(7,204) |
(37,803) |
(38,308) |
(61,613) |
||
Working capital |
1,524 |
3,274 |
(2,325) |
4,122 |
||
Exceptional & other |
(109) |
(5) |
1,320 |
1,933 |
||
Tax |
0 |
0 |
0 |
0 |
||
Net operating cash flow |
|
|
(5,789) |
(34,534) |
(39,313) |
(55,558) |
Capex |
(374) |
(291) |
(195) |
(224) |
||
Acquisitions/disposals |
(81) |
(9) |
(11,801) |
(11,801) |
||
Net interest |
0 |
0 |
0 |
0 |
||
Equity financing |
31,364 |
33,061 |
42,320 |
0 |
||
Dividends |
0 |
0 |
0 |
0 |
||
Other |
(68) |
(36) |
0 |
0 |
||
Net Cash Flow |
25,052 |
(1,809) |
(8,989) |
(67,583) |
||
Opening net debt/(cash) |
|
|
0 |
(25,052) |
(22,544) |
(12,598) |
FX |
0 |
0 |
(979) |
0 |
||
Other non-cash movements |
0 |
(699) |
22 |
0 |
||
Closing net debt/(cash) |
|
|
(25,052) |
(22,544) |
(12,598) |
54,985 |
Source: ASLAN reports, Edison Investment Research
|
|
The restructuring initiated in FY17 started to benefit the group in Q218 and Snakk Media finally returned to profit in its second half. Revenues for FY18 were close to the prior year at NZ$10.3m (NZ$10.6m), with increased self-service mobile advertising revenues offset by a decline in business in Southeast Asia (where overheads have been pared back). The cost base in FY19e will be lower with the full-year benefit. The group had year-end cash of NZ$1.1m, just below the current market capitalisation of NZ$1.3m.