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Research: Healthcare
On 3 December, RedHill announced positive top-line data for its second Phase III study for TALICIA in first-line Helicobacter pylori infection. With the focus now on final data, expected NDA submission (H119), approval and launch (potentially H219), TALICIA is one of the key value drivers for RedHill in the short term. The December share issue of $20m should ensure a smooth TALICIA launch, provide working capital for a pivotal Phase III nontuberculous mycobacteria trial, preparation for a Phase III trial in Crohn’s disease and support the commercial US organisation. Our updated valuation is $491m (NIS1.82bn), or $17.3/ADS (NIS6.4/sh).
Written by
RedHill Biopharma |
TALICIA Ph III top-line data positive |
R&D update |
Pharma & biotech |
19 December 2018 |
Share price performance
Business description
Next events
Analysts
Redhill Biopharma is a research client of Edison Investment Research Limited |
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On 3 December, RedHill announced positive top-line data for its second Phase III study for TALICIA in first-line Helicobacter pylori infection. With the focus now on final data, expected NDA submission (H119), approval and launch (potentially H219), TALICIA is one of the key value drivers for RedHill in the short term. The December share issue of $20m should ensure a smooth TALICIA launch, provide working capital for a pivotal Phase III nontuberculous mycobacteria trial, preparation for a Phase III trial in Crohn’s disease and support the commercial US organisation. Our updated valuation is $491m (NIS1.82bn), or $17.3/ADS (NIS6.4/sh).
Year end |
Revenue ($m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
12/16 |
0.1 |
(29.4) |
(0.23) |
0.0 |
N/A |
N/A |
12/17 |
4.0 |
(45.5) |
(0.26) |
0.0 |
N/A |
N/A |
12/18e |
9.5 |
(40.0) |
(0.16) |
0.0 |
N/A |
N/A |
12/19e |
12.4 |
(43.5) |
(0.15) |
0.0 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles and exceptional items.
TALICIA met primary endpoint: 84% eradication
According to the top-line data, TALICIA achieved an 84% eradication rate in the treatment group vs 58% in the active comparator (p<0.0001), was safe and well tolerated. While, final data is still to be released (H119); we believe it is likely, and in line with preliminary company plans, that RedHill will be able to submit an NDA with the FDA in H119. The review process should be fast due to Qualified Infectious Disease Product (QIDP) designation, which grants a priority review. If approved, we expect some sales to be achieved quickly due to RedHill’s established commercial platform. Our model includes revenues in 2020, but some initial sales could be booked in 2019. The 2017 ACG Guidelines describe rifabutin triple therapy as a salvage treatment, citing ‘moderate quality of evidence’, rifabutin cost and rare but serious safety concerns, but notes a very low H. pylori resistance rate to rifabutin. RedHill’s Phase III programme (two large trials) should address any data-quality concerns and the safety profile appears excellent at the doses used in the trial.
Financials: $20m gross extends cash into 2020
The recent share issue brings our end-2018 cash estimate to $53m. According to our model, this should cover RedHill’s operating activities into 2020 (we do not yet include sales from TALICIA ahead of the FDA review process). Q318 revenues from the commercialised gastrointestinal (GI) products were $2.2m (vs $2.4m in Q218). We have revised our mid-term sales estimates down (2018 and 2019 estimates now at $9.5m vs $12.4m and $12.4m vs $30.2m, respectively), but increased long-term gross margin to 65% from 50%, resulting in a slight net negative effect.
Valuation: Revised to $491m or $17.3 per ADS
Our revised valuation of RedHill is $491m or $17.3/ADS vs $432m or $16.9/ADS. The increase is due to the increased probability of success for TALICIA (90% vs 70%), improved cash position after the share issue and moving TALICIA’s launch to 2020 from 2021, which were partially offset by reduction in GI product sales estimates. Near-term catalysts for the share price are TALICIA final data, NDA submission to the FDA in H119 and potential FDA approval in H219.
TALICIA Phase III top-line readout
The top-line results from the TALICIA confirmatory Phase III study in first-line treatment of H. pylori infection regardless of ulcer status were announced on 3 December 2018. They show that the primary endpoint has been met, which was the H. pylori eradication rate with TALICIA vs active comparator of amoxicillin + omeprazole. The TALICIA treatment group achieved an 84% eradication rate (n=228) vs 58% with the active comparator (n=227) with a high level of significance (p<0.0001). In addition, TALICIA was found to be safe and well tolerated, which is key because the main safety issues seen with rifabutin were not observed in the study. This is likely due to the lower doses used in the study, as concerns about rifabutin toxicity (myelotoxicity) mainly come from treating other infections and using higher doses. The secondary endpoints and final results should be released early in 2019 and RedHill should be able to submit an NDA with the FDA in H119. As a reminder, after the first Phase III study (n=188) TALICIA delivered positive final results in March 2016, which showed that TALICIA eradicated H. pylori in 89.4% of patients (p<0.001) and 63% in subsequent open-label treatment of the placebo arm patients in the same trial.
Rifabutin as part of combination of generic therapy is already used for the treatment of H. pylori as a salvage therapy, although it has not been approved by the FDA specifically for this indication. The therapy has been found to be very effective at H. pylori eradication. This may partly explain the muted share price reaction after the TALICIA data announcement. The 2017 ACG Guidelines describe rifabutin triple therapy as a salvage treatment and cites ‘moderate quality of evidence’, the generic rifabutin cost and rare but serious safety concerns, but notes a very low H. pylori resistance rate to rifabutin. We believe RedHill’s Phase III programme (two large trials) should address any data quality concerns and the safety profile appears to be excellent at doses used in the trial. If approved by the FDA, TALICIA will also be the only rifabutin-based therapy with an H. pylori eradication indication included in its label.
As RedHill described in its recent R&D call on TALICIA, there were previous attempts to introduce branded therapies for H. pylori eradication (Pylera and Prevpac), which corresponded to first-line generic combination therapies. While initially successful, these drugs failed to achieve sustained growth because they mainly offered convenience, but still suffered from the same increasing resistance issue as the generic combination therapies, which successfully eradicate H. pylori in 60–70% of cases. This has been decreasing constantly over the last couple of decades and RedHill’s trial showed a 58% success rate in the active comparator arm against amoxicillin plus omeprazole, which is one of the first-line options. In addition, RedHill’s first Phase III study showed 63% efficacy of standard-of-care therapies in a subsequent open-label part of the study, while the confirmatory Phase III study showed 64% efficacy of standard of care in the subsequent open-label part. Therefore, with the Phase III data in hand and against this background of increasing in H. pylori resistance rates against front-line therapies, RedHill is well positioned to influence clinical practice, although it is never an easy task. Notably, RedHill’s Phase III trial was designed as front-line therapy regardless of ulcer status, which, if approved by the FDA, opens up the broadest possible target population. Prevpac and Pylera are approved for patients with diagnosed ulcers, which is a substantially smaller target population.
RedHill has also collected data on antibiotic resistance rates during the US study. This data shows similar rates to those summarised in the recent ACG Guidelines published in 2017 (from two separate studies on samples of the US population) (Exhibit 1). Both sets of resistance rates show a significantly lower resistance to rifabutin and amoxicillin than clarithromycin and metronidazole, supporting the use of rifabutin and amoxicillin as alternatives.
Exhibit 1: H. pylori antibiotic resistance rates in the US (%)
Antibiotic |
2009 – 2011* (ACG Guidelines 2017) |
2017 – 2018** (RedHill) |
Metronidazole |
20 |
45 |
Clarithromycin |
16 |
17 |
Levofloxacin |
31 |
- |
Tetracycline |
<2 |
- |
Amoxicillin |
<2 |
6 |
Rifabutin |
<2 |
0 |
Source: *American Journal of Gastroenterology Clinical Guideline: Treatment of Helicobacter pylori Infection (2017); Shiota S, Reddy R, Alsarraj A et al. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clin Gastroenterol Hepatol 2015; 13:1616–24; Gisbert JP, Calvet X. Review article: rifabutin in the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther 2012; 35:209 – 21; **RedHill ERADICATE Hp2 Phase III study
Next steps
RedHill expects to present the full data at a conference in early 2019 and submit an NDA application to the FDA in H119. As mentioned, TALICIA has QIDP designation from the FDA, which endows both fast-track development and priority review status and, according to management, this could lead TALICIA to be approved in H219. If approved, RedHill plans to use its existing commercial platform to market TALICIA to gastroenterologists and expects a minimal incremental cost of launch. Theoretically this should allow RedHill to quickly leverage this platform to achieve initial sales as soon as H219, with all 40 US sales reps expected to be engaged in the TALICIA commercial launch. Worth noting that the company can increase the salesforce as necessary. Commercial manufacturing is already in scale-up mode and RedHill is ready to start discussions with payors. In our view, RedHill’s commercialisation to gastroenterologists is sensible as this community is much smaller than primary care physicians, which makes it easier to promote TALICIA. However, to access the broader patient pool, we believe RedHill will consider how to market to primary care physicians. One option could be a co-promotion partner, but no concrete announcement has been made in this regard yet.
Exhibit 2: Eradication rates of regimens for H. pylori treatment (TALICIA contains omeprazole + amoxicillin + rifabutin)
Regimen |
Components |
Use |
Eradication (%) |
Disadvantages |
Standard triple therapy |
PPI + clarithromycin + amoxicillin (or metronidazole) |
First line in areas of low CAM resistance |
60-70% (14% in resistant strains) |
Widespread clarithromycin resistance |
Bismuth quadruple therapy |
PPI + bismuth + tetracycline + metronidazole |
First line in areas of > 20% CAM resistance. Second line when triple therapy fails. |
c 80% |
Bismuth has some toxicity issues; complex dosing, many tablets. Metronidazole resistance has some impact on efficacy of bismuth but to a lesser extent than clarithromycin with standard triple therapy. |
Sequential therapy, |
Dual therapy; PPI + amoxicillin followed by triple therapy; ppi + clarithromycin + metronidazole |
As above |
c 70% in CAM resistant strains (40% in dual resistant strains) |
Dual resistance problems |
Levofloxacin-based triple therapy, (10d) |
PPI + levofloxacin + amoxicillin |
Second or third line. Broad-spectrum quinolone used to overcome CAM resistance. |
c 90% |
Quinolone resistance increasing (40% in US, 20% Europe, 10% Asia) |
Rifabutin-based triple therapy, (7–14d) |
PPI + amoxicillin + rifabutin |
'Rescue' treatment |
67–91%, Gisbert et al 89.4%, RedHill first Phase III data 84% RedHill confirmatory Phase III data |
Rifabutin has rare side effects (myelotoxicity, ocular toxicity), although RedHill did not encounter significant side effects; the TALICIA PK/PD profile is different as the rifabutin dose is divided into three 50mg pills per day. |
Source: Adapted from V. Papastergiou et al and C Fallone et al.
Note: PPI: proton pump inhibitor (lansoprazole/ rabeprazole/ esomeprazole) at standard dose; CAM: clarithromycin.
Financials and valuation
On 11 December 2018, RedHill announced the closing of an ADS share issue for $20m (gross). In total, 2,857,143 ADS were issued at a price of $7.00 (28,571,430 ordinary shares). RedHill also granted the underwriters a 30-day option to purchase up to an additional 15% (428,571) ADS (expiring on 10 January 2019). At the end-September Q318 cash and cash equivalents were $43m. This and the new funds, according to our model, should cover RedHill’s operating activities into 2020, which includes the TALICIA’s launch, a new trial in NTM, and preparation for another trial in Crohn’s disease.
Q318 revenues from the commercialised GI products were $2.2m (vs $2.4m in Q218). The reported gross profit margin improved again in Q318 to 73% vs 69% in Q218. The operating loss was $9.7m vs $13.9m in Q317 following the implementation of the cost-cutting programme. Q318 R&D costs were $6.6m versus $8.1m a year ago. Cash burn in the quarter was at the target $8.5m average rate per quarter for 2018.
We have revised down our near- to mid-term sales estimates (2018 and 2019 estimates now at $9.5m vs $12.4m and $12.4m vs $30.2m, respectively). RedHill has consistently posted a stronger gross margin for its product portfolio (we had assumed 50%), and have therefore increased it to 65% in our model; this could be even higher if the level booked in Q3 results holds. The overall net effect from this revision on our calculated NPV of the commercial business was slightly negative.
Our RedHill valuation has increased to $491m or $17.3/ADS from $432m or $16.9/ADS. This is mainly due to the increase in probability of success of TALICIA, increased cash position and moving the launch date of TALICIA from 2021 to 2020 in our model. Our detailed assumptions for each of the indications are discussed in our last outlook report. Final data, NDA submission to the FDA in H119 and potential FDA approval in H219 of TALICIA for H. pylori are other potential catalysts in the near term.
Exhibit 2: Sum-of-the-parts RedHill valuation
Product |
Launch |
Peak sales ($m) |
NPV ($m) |
NPV/share ($) |
Probability |
rNPV ($m) |
rNPV/share ($) |
TALICIA, - H. pylori infection |
2020 |
86 |
132.6 |
4.7 |
90% |
118.6 |
4.2 |
RHB-104, - Crohn’s disease |
2023 |
145 |
72.5 |
2.6 |
50% |
30.6 |
1.1 |
- NTM infections |
2022 |
50 |
59.6 |
2.1 |
30% |
15.0 |
0.5 |
BEKINDA, - Gastroenteritis |
2022 |
21 |
30.2 |
1.1 |
85% |
25.2 |
0.9 |
- IBS-D |
2023 |
201 |
147.1 |
5.2 |
60% |
107.5 |
3.8 |
YELIVA, - Cholangiocarcinoma |
2024 |
115 |
170.2 |
6.0 |
10% |
11.3 |
0.4 |
- r/r MM |
2025 |
565 |
260.7 |
9.2 |
10% |
64.9 |
2.3 |
- Advanced HCC |
2025 |
649 |
156.1 |
5.5 |
10% |
47.7 |
1.7 |
GI specialty products: Donnatal, EnteraGam & Esomeprazole |
Market |
48 |
17.6 |
0.6 |
100% |
17.6 |
0.6 |
Net cash (est. end-2018) |
52.5 |
100% |
52.5 |
1.9 |
|||
Valuation |
1,099.1 |
36.9 |
490.7 |
17.3 |
|||
Source: Edison Investment Research. Note: WACC = 12.5% for product valuations. IBS-D: irritable bowel syndrome; r/r MM: refractory/relapse multiple myeloma; HCC: hepatocellular carcinoma; NTM: nontuberculous mycobacteria.
Exhibit 3: Financial summary
$000s |
2016 |
2017 |
2018e |
2019e |
||
December |
IFRS |
IFRS |
IFRS |
IFRS |
||
PROFIT & LOSS |
||||||
Revenue |
|
|
101 |
4,007 |
9,501 |
12,351 |
Cost of Sales |
0 |
(2,126) |
(3,135) |
(4,323) |
||
Gross Profit |
101 |
1,881 |
6,366 |
8,028 |
||
Research and development |
(25,241) |
(32,969) |
(25,920) |
(29,084) |
||
EBITDA |
|
|
(30,499) |
(51,891) |
(39,911) |
(41,556) |
Operating Profit (before amort. and except.) |
(30,543) |
(51,972) |
(30,543) |
(51,972) |
||
Intangible Amortisation |
0 |
0 |
0 |
0 |
||
Exceptionals |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
||
Operating Profit |
(30,543) |
(51,972) |
(40,018) |
(41,687) |
||
Net Interest |
1,173 |
6,428 |
0 |
0 |
||
Profit Before Tax (norm) |
|
|
(29,370) |
(45,544) |
(40,018) |
(41,687) |
Profit Before Tax (reported) |
|
|
(29,370) |
(45,544) |
(40,018) |
(41,687) |
Tax |
0 |
0 |
0 |
0 |
||
Profit After Tax (norm) |
(29,370) |
(45,544) |
(40,018) |
(41,687) |
||
Profit After Tax (reported) |
(29,370) |
(45,544) |
(40,018) |
(41,687) |
||
Average Number of Shares Outstanding (m) |
128.5 |
128.5 |
175.3 |
248.0 |
||
EPS - normalised (c) |
|
|
(0.23) |
(0.26) |
(0.16) |
(0.15) |
EPS - normalised |
|
|
(0.24) |
(0.26) |
(0.16) |
(0.15) |
EPS - (reported) ($) |
|
|
(0.23) |
(0.26) |
(0.16) |
(0.15) |
Dividend per share (c) |
0.0 |
0.0 |
0.0 |
0.0 |
||
Gross Margin (%) |
100.0 |
46.9 |
67.0 |
65.0 |
||
EBITDA Margin (%) |
N/A |
N/A |
N/A |
N/A |
||
Operating Margin (before GW and except.) (%) |
N/A |
N/A |
N/A |
N/A |
||
BALANCE SHEET |
||||||
Fixed Assets |
|
|
6,397 |
5,667 |
6,211 |
6,995 |
Intangible Assets |
6,095 |
5,285 |
5,820 |
6,605 |
||
Tangible Assets |
165 |
230 |
239 |
238 |
||
Investments |
137 |
152 |
152 |
152 |
||
Current Assets |
|
|
67,815 |
51,676 |
57,428 |
29,265 |
Stocks |
0 |
653 |
653 |
653 |
||
Debtors |
1,661 |
4,818 |
4,270 |
4,270 |
||
Cash |
53,786 |
16,455 |
28,163 |
0 |
||
Other* |
12,368 |
29,750 |
24,342 |
24,342 |
||
Current Liabilities |
|
|
(5,356) |
(11,830) |
(11,521) |
(11,521) |
Creditors |
(5,356) |
(11,830) |
(11,521) |
(11,521) |
||
Short-term borrowings |
0 |
0 |
0 |
0 |
||
Long-Term Liabilities |
|
|
(6,155) |
(448) |
(2,536) |
(14,610) |
Long-term borrowings |
0 |
0 |
0 |
(12,074) |
||
Other long-term liabilities |
(6,155) |
(448) |
(2,536) |
(2,536) |
||
Net Assets |
|
|
62,701 |
45,065 |
49,582 |
10,130 |
CASH FLOW |
||||||
Operating Cash Flow |
|
|
(28,258) |
(44,769) |
(35,350) |
(39,321) |
Net Interest |
0 |
0 |
0 |
0 |
||
Tax |
0 |
0 |
0 |
0 |
||
Capex |
(85) |
(146) |
(116) |
(131) |
||
Acquisitions/disposals |
0 |
0 |
0 |
0 |
||
Financing |
36,017 |
25,653 |
42,300 |
0 |
||
Other** |
24,596 |
(18,069) |
4,873 |
(785) |
||
Dividends |
0 |
0 |
0 |
0 |
||
Net Cash Flow |
32,270 |
(37,331) |
11,708 |
(40,236) |
||
Opening net debt/(cash) |
|
|
(21,516) |
(53,786) |
(16,455) |
(28,163) |
HP finance leases initiated |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
||
Closing net debt/(cash) |
|
|
(53,786) |
(16,455) |
(28,163) |
12,074 |
Source: Edison Investment Research, RedHill accounts. Note: *Bank deposits and financial assets at fair value. **Includes bank deposits converted to cash and cash equivalents.
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Research: Metals & Mining
For the second time in less than a month, Endeavour has announced the delineation of a c 1Moz maiden resource – in this case, at Kari Pump, 7km west of the Houndé processing plant in Burkina Faso. As at Fetekro, the majority (98.0%) of the resource has been classified into the indicated category of resources. More significantly, the average grade of the maiden Kari Pump resource is at a 31.8% premium to the average of the pre-existing Houndé resource and a 44.3% premium to the average of the pre-existing Endeavour resource, with further potential upside in the region.