Andrew Pannu
@andrewpannu
Followers
12K
Following
626
Media
228
Statuses
898
daily dose of biotech & healthcare commentary • founder @sleuthinsights • building software for the bioeconomy
LA / Bay Area
Joined October 2013
The best biopharma M&A deals (with assets still contributing meaningfully in 2022). I analyzed the pipeline of 27 big pharma and 27 acquired companies to find the asset-driven deals with the highest ROI . Summary below:.
18
32
218
Gene therapy landscape. I pulled together 42 public companies and charted the preclinical & clinical assets of each, segmented by approach & vector. Some takeaways:
30
195
1K
Gene editing landscape. I pulled together 42 public & private companies and charted the preclinical & clinical assets of each, segmented by approach & editor. Some takeaways:
18
150
673
RNA therapies market map. 124 companies are segmented by approach and highest stage of development. Some takeaways:
24
155
657
Gene therapy landscape. Pulled together 42 companies and charted the preclinical and clinical assets of each, segmented by approach and vector. Some takeaways:
15
76
390
Why pharma has stayed away from cell therapy M&A. Exhibit 1: IPO and M&A Activity from 2013 to today. The dominant strategy has evolved alongside the broader capital markets: . Early on we saw more transformative M&A (Gilead / Kite in 2017, Celgene / Juno in 2018), while
14
65
370
Biotech sales forecasts are wildly off for most drugs. I took a look back at projected 5-year sales for novel drugs from the class of 2013 to the class of 2018 and compared them with actual performance. As you can see below, there are only a few instances where the variance was
23
56
347
Obesity Market Overview. A deep dive into the unmet need, competitive landscape and future of treatment:
11
60
340
Is the best yet to come for cell therapy?. I pulled together 45 companies in the space and charted the preclinical and clinical assets of each, segmented by cell source and modality. Exhibit 1: Cell Therapy Landscape. Some thoughts:. The above is just a snapshot - an attempt to
16
67
338
The ADC space is blowing up:. • >$125B in partnerships and M&A since 2019, including Pfizer's $43B acquisition of $SGEN and a record $5.5B upfront deal ($MRK / Daiichi) this year.• Hundreds of assets across thousands of trials.• 8 approvals in the last 5 years (13 total). I
18
71
331
When you read posts like this, it's clear that the biopharma industry has done a terrible job communicating the value prop of our industry. A reminder on some of those points:. Grab a coffee, this will be a long one. ✔️ Drug spending is far less than hospital care & physician
The U.S. has the highest drug prices in the world. And to keep it that way, pharma companies are suing to block a program that grants Medicare the ability to negotiate pricing. This ability was glossed, ironically, as “tantamount to extortion” by Merck. How did we get here?
11
62
318
How Merck built a blockbuster with Keytruda:. 39 FDA approvals across 16 tumor & 2 tumor-agnostic indications on the road to an estimated >$30B in annual sales by 2028. And expect more coming: $MRK is running >1K pembrolizumab trials (incl. 400+ combo trials & 80+ registrational
14
65
317
How much of pharma's top assets are acquired vs. developed in-house? . Across 14 companies, on average about 3/5 (60%) were either licensed or brought in via an acquisition, with smaller biotechs being the most common source. Some other observations:
11
57
292
Cell therapy landscape 🧬. I pulled together 44 companies with a range of approaches & segmented assets by development phase. Let's take a deeper look
8
60
296
Biotech Math (Pharma Edition). Or, how the blockbuster model impacts everything in the industry. First, let's gather some data for the top 10 pharma companies:. It's clear these businesses have incredible leverage: a 3.5% increase in revenue translates to a ~8% increase in net
12
55
290
EGFRm+ NSCLC treatment landscape. Key assets, trials and companies segmented by treatment line and mutation type. Some takeaways from this competitive space:
8
78
279
Being first-in-class matters a lot. Prior analyses have shown that timing is the most important factor for commercial performance, even ahead of therapeutic value. But when have late entrants ended up dominating the market, and what did they do differently?. I pulled together
17
39
265
Cell therapy is in the middle of a huge shift. and everyone from small biotechs to big pharma want in on the next big thing: autoimmune disorders. Here's how I think this goes down:. First, I charted the programs of 37 companies in this space, segmented by cell source and
21
40
252
Competitive landscape for targeted therapies in oncology (TO). 425 assets across 19 pharma companies, segmented by tumor type, phase of development, modality and ownership. If you'd like a PDF copy or if I missed any key assets, let me know below!. Some takeaways & stats:
45
50
249
Overview of gene editing approaches & select key players . Source: Piper Sandler
9
48
246
A primer on psychedelics in drug development 🍄. Digging into the emerging science, competitive landscape and convoluted path to market. Let's take a trip:
10
36
241
2024 FDA Novel Drug Approvals (with segmentation by manufacturer, indication and supporting clinical trials). The agency has approved 55 novel drugs so far, with 47 via CDER and 8 via CBER. Other takeaways:.• This is 22% behind 2023 which saw 71 approvals (16 CBER, 55 CDER) -
18
49
237
Something biotechs tend to underestimate: the indication you pick dictates your commercial strategy. Most focus on the clinical profile of their drug, but in "payor-managed" indications, understanding the incentives of PBMs & other middlemen can make or break a launch (even if
18
22
234
Cell therapy market map . Segmented by approach and highest development phase. • 150+ companies with disclosed pipelines and 600+ programs in development.• Space is still early - only a few pivotal stage programs.• Continued commercial PoC will drive further investment $LEGN
14
40
227
Well said. I'll add that effective drugs suffer from the silent hero problem that Taleb wrote about in The Black Swan. Many can prevent far worse downstream outcomes (hospitalization, surgeries, chronic pain, early death), but we don't tend to reward acts of prevention like we do.
Drug industry’s popularity is thanks to its own success. If you have a disease for which there is a medicine, you don’t know anything other than the bill at the pharmacy counter. If you have a disease without a cure, all your faith is put into the drug industry because no one
8
39
208
Analysis of Big Pharma Therapeutic M&A Deals from 2019 to today. Some takeaways: . • M&A tends to pick up as company's approach big LOEs, and so unsurprisingly, Merck and AbbVie led the way. For Merck, they're facing a $30B LOE in 2028 with Keytruda - big bets on Acceleron
17
46
209
Alzheimer's Competitive Landscape 🧠 . a deep dive into the unmet need and future of treatment:
12
55
190
ADCs are hot right now, but amongst big pharma, not everyone has jumped in with the same enthusiasm. I took a look at the oncology portfolios of the largest pharma companies and charted key assets by development stage. Exhibit 1: Uneven ADC Exposure Within Big Pharma. Some
7
27
191
How is pharma replacing upcoming LOEs?. The scale of that problem has never been higher, with >$200B of sales at-risk through 2028. After analyzing the pipelines, management commentary and BD maneuvers of key pharma players, here are some thoughts on how this plays out:. Exhibit
5
47
187
Biotech has a consolidation problem. other insights from an analysis of >$1B biopharma M&A deals since 2019:. Exhibit 1: YoY deal volume / value + % of deals by development stage & modality. We've seen a noticeable dip in >$1B deals this year, although deal value is in-line
4
34
178
Everywhere you look in biopharma, you see drug duopolies. But why is this such a common structure? . Some thoughts below. If you'd like a PDF of the graphics, comment below or download it for free from Sleuth's website! . 1. As long as they're not tasked with building market
9
25
180
Refreshed obesity competitive landscape. Updated thoughts on this massive market following today's positive SELECT trial readout ($NVO) and Mounjaro sales beat ($LLY):
6
29
166
Notable LOEs through 2028 (with at-risk revenue estimates). $BMY, $MRK, $JNJ and $ABBV among the most impacted. With >$175B in cumulative sales at-risk & record amounts of cash on hand, the stage appears set for a rebound in M&A
7
33
164
How has pharma capitalized on the AI boom? .Partnerships. The number pharma / AI partnerships over the past few years has exploded as awareness, access and proof-of-concept milestones have all accelerated. This has been driven both within biopharma (i.e. breakthroughs such as
3
22
163
Eli Lilly is in a unique position to break out of the Pharma LOE cycle - at least for now. Consensus is that tirzepatide (Zepbound / Mounjaro) will be the biggest drug of all time, topping $70B in sales by 2030. But, unlike other durable mega-blockbusters like Keytruda ($30B+) or
16
22
169
A deep dive into neuropsychiatric therapeutics. • Competitive landscape.• Emerging treatments.• Key concerns.& more. Exhibit 1: late-stage competitive landscape across key indications. The global disease burden for these indications is immense, with >50M total patients &
6
38
160
Separate from this specific case, the FTC's view of pharma is that their focus on partnering / M&A is driven (at best) by their own R&D inefficiency or (more likely) nefarious purposes, such as tiller acquisitions or price fixing. They look at the top 20 pharma companies and.
I'm a little baffled by what the FTC is doing here. Doesn't this just make it less likely that companies will do licensing deals? A company that is already in a space is the most likely to license a new entrant.
8
30
146
IBD competitive landscape & disease primer. Exploring the highly competitive space on the heels of Merck's $10.8B acquisition of Prometheus $RXDX
5
26
146
Radiopharmaceuticals market map ☢️. 66 companies are segmented by radioisotope and highest stage of development. Further thoughts on this emerging market below:. *After a brief hiatus, we'll be back to regular breakdowns & thought pieces here*
5
32
143
Top public M&A targets for 2023 (based on sell-side consensus / my opinion):. Small-Cap: $VRNA, $AUPH, $MIRM, $RIGL. Mid-Cap: $ASND, $KRTX, $APLS, $MDGL, $ALKS, $ITCI, $MRTX, $PRTA, $AMLX, $XENE, $KRYS. Large-Cap: $ALNY. Excludes active / rumored takeout targets
11
27
136
Pancreatic cancer treatment landscape - mapping key completed and ongoing clinical trials by treatment line. A few takeaways on how the industry is tackling this extremely difficult-to-treat disease:. #1 This is arguably the deadliest cancer in the US - some morbid stats:. • On
8
16
133
It's been 2+ years since the IRA was signed into law - has Pharma shifted away from small molecule R&D and M&A in that time?. I analyzed the % of small molecule vs. biologic M&A deals from '13-'21 vs. '22-'24 + pharma's current small molecule asset count by dev stage. Takeaways:
2
21
132
Grading 10 notable single-asset driven M&A deals from 2016-2019. Some takeaways:.• Goes without saying, BD is tough. Not only do you have to manage clinical risk, but even if the asset works well, you could get steamrolled by a slightly better positioned competitor or be unable
4
19
130
Got some great feedback and wanted to share a slightly revised version with everyone. Changes:.- Removed Lava Therapeutics.- Added ArsenalBio.- TIL legend icon in auto. Will add additional companies in future versions. If you had asked for a PDF previously, check your DMs
Cell therapy landscape 🧬. I pulled together 44 companies with a range of approaches & segmented assets by development phase. Let's take a deeper look
16
23
126
Duchenne muscular dystrophy (DMD) deep-dive. • Disease profile.• Competitive landscape.• Pipeline highlights.• Reimbursement. Let's dig in:
4
17
125
Benchmark of approved CAR-T therapies efficacy by indication
1
23
125
Timing and size of LOEs for the top Pharma products by 2024E sales. A significant portion of current Pharma revenue comes from drugs with medium-term LOE risk (i.e. by 2028). Some takeaways as we head into JPM:
6
24
121
If you're investing in radiopharmaceuticals, you should study the parallels with cell therapy. In both, the supply chain is the key limitation. If you'd like PDFs of the graphics below, comment below! Some takeaways:
4
19
117
Cell Therapy Supply Chain Market Map. Segmented 49 companies by stage throughout this vein-to-vein process. Some thoughts on the complexity of bringing these medicines to patients:
5
20
112
Snapshot of cell therapy M&A and IPO activity from 2013- 2022 YTD. select 2022 private financings and recent BD deals:
3
23
108
Cash runway for select rare disease companies. Majority have >2 years of cash. Source: Leerink
3
16
110
Public market performance of AI-enabled drug developers (a subset of the #TechBio space). How they've performed (and why they've struggled):.
7
14
96
Summary of emerging tech to potentially improve earlier generations of CAR-T in heme and solid tumor indications . Source: Guggenheim
4
23
90
The competition amongst CDK4/6 inhibitors within mER+ breast cancer is an interesting case study on how flawless execution is needed in today's markets. Exhibit 1: mER+ Breast Cancer Treatment Landscape. First, a brief history of this space:.• ~65-70% of all breast cancers are
4
8
91
While consensus is growing against PBM's rebate practices that drive higher drug prices & legislation (i.e. PBM Reform Act) is emerging, the reality is that most PBMs saw the writing on the wall and have changed their businesses to get ahead of legislation. Here's what I mean:
In light of the fact that the US leads the world in health care costs as a % of GDP without better outcomes, I would love to hear the argument from someone in pharma why we should be OK that we pay multiples of the same price in other countries for the same drug?.
3
14
84
What is the status of the top-selling drugs for Medicare price negotiation? . The top 25 drugs by 2021 Medicare sales are profiled below. Some thoughts:
3
18
87
Humira near-term US biosimilar launches. 10+ competitors will be launching in 2023, aiming ~$19B of 2022E revenue. We haven't seen a biologic of Humira's scale face biosimilar competition yet, so the resulting market dynamics will be interesting. Some takeaways:
4
14
87
Top 10 drugs to watch heading into 2023 (for drugs first approved in 2022). Ranked by sell-side 2027 sales estimates, which may reflect more than 1 indication (i.e. Mounjaro reflects obesity + T2D). $LLY leads the way with Mounjaro, with $BMY second ($5.8B) based on 3 approvals
3
23
77
List of 2022 FDA approvals with estimated sales from 2022-2027. Source: Needham
2
15
82
Cell therapy efficacy in solid tumors. TIL & TCR therapies are the furthest along, with CAR-based therapies in early stages. Source: Guggenheim
6
12
78
Snapshot of M&A and IPO activity from 2013 - 2024 YTD in the ADC space. A few takeaways:
2
20
78
Neuro-oncology treatment landscape. Key assets, trials and companies targeting brain & spinal tumors, segmented by treatment line. Some thoughts on a difficult space:
1
19
75
Asthma & COPD competitive landscape 🫁. commentary on the disease background, current standard of care and evolving market dynamics:
3
10
67
ADC remains 🔥🔥🔥. With $ABBV's ~$10B acquisition of $IMGN today, the # of independent late-stage ADC players thins again (to go along with Pfizer / SeaGen and Merck / Daiichi). At this point, the biggest names are accounted for. ~$2B in WW consensus peak sales for Elahere.
The ADC space is blowing up:. • >$125B in partnerships and M&A since 2019, including Pfizer's $43B acquisition of $SGEN and a record $5.5B upfront deal ($MRK / Daiichi) this year.• Hundreds of assets across thousands of trials.• 8 approvals in the last 5 years (13 total). I
5
6
72
Key events in gene editing therapeutic development. Clinical progress has driven the field forward. Source: Piper Sandler
6
19
68
Biotech is a throwback to older equity markets. A historical feature of the biotech equities markets has been companies at the forefront of large emerging TAMs going public relatively early in their history. For them, an IPO is an essential financing to access broader.
4
8
69
List of single-product, late-stage companies - characteristics that are the common profile of M&A targets. Divided by small molecule & biologics. Source: EVRISI
1
12
68
How have big pharma valuations trended before and after some of the biggest LOEs the industry has seen? Surprisingly, pretty well. (powered by @sleuthinsights). First, some quick stats. On average, these drugs represented ~28% of US sales just prior to LOE. All were in the hands
3
5
67
Notable 2023 US drug approvals ranked by 2027 sales estimates. $LLY leads the way with 4 entries. CNS is well represented (MDD, Alzheimer's, Parkinson's)
4
11
65
5-Year Survival Rate of Cancers With >100K Incidence (US). Some high-level observations:.• Cancers with the highest unmet need (high incidence, low survival) are generally a graveyard of failed treatments - lack of efficacy in pancreatic or liver cancer, for example, has been
2
14
61
Key regulatory and data catalysts for Alzheimer's in 2023. Source: Leerink
7
19
59
History of ADC (antibody-drug conjugate) development. First clinical trial was in 1983, with first approval in 2000 (Mylotarg - Pfizer). Now has 12 FDA approvals (excl. Blenrep), with 8 in the last 5 years
1
17
60
My view on the top acquirers for $MDGL after yesterday's stellar data announcement in NASH. key late-stage pipeline assets in NASH & catalysts through 2023 & beyond:
3
7
60
% of M&A deals by development stage. Pharma is still predominately buying de-risked late-stage or commercial assets, particularly when looking at public company deals only. Source: Needham
0
10
61
Cell therapy programs and their progress by clinical phase
2
13
60
Select biopharma pipeline readouts to watch in 2023-2024. Source: Leerink
2
8
58
Breakdown of programs in the cell therapy space. Source: WB
1
4
60
Another layer here is branded vs unbranded platforms. The former was what we saw a lot of during the easy financing environment of 2019-2021 - explicitly marketing the company around a novel, scalable technology or approach. A natural next step for these companies is to.
1. platforms were favored in 2019-2021, but since 2021, venture financing has favored assets over platforms. 2. as much as I would love to see pharma M&A as an exit path for biotech platforms in addition to IPO, there is little enterprise value of a platform acquisition for.
2
6
58
A $50B CHIPS-like Act for Domestic Drug Manufacturing?. The number of active drug shortages in the US is at a 10+ year high:. Why? Mainly the economics of generics (note: biosimilars are different):.- Manufacturers face severe margin compression, with >80% price cuts as multiple
6
8
53
Select AI partnerships / collaborations by big pharma. Clear shift in sentiment from healthy skepticism to strategic integration over the past few years. High-profile deals in the last 2 years:.- Sanofi / Atomwise.- $BMY / $EVO.- Sanofi / $EXAI.- Amgen / Generate.- Roche / $RXRX
1
9
56
Breakout of CAR-T sales from Q1'18 to Q3'22 by indication (DLBCL, MM, MCL). On track to show ~$3B annualized RR in 2022, with 55% YoY growth
2
6
52
M&A commentary from select big pharma . - Robust deal capacity across the board.- $PFE (40% of 2022 sales) / $MRK (Keytruda) have major LOE gaps to fill this decade.-Recent focus has been on de-risked clinical / commercial assets.- Most looking to expand current TA leadership
2
3
52
Landscape of obesity drug on-ramp providers. Mapping out the emerging ecosystem built around the massive demand for GLP-1 weight loss drugs, such as Wegovy / Ozempic & Mounjaro. Some thoughts on how this space evolves:
3
11
50
Amongst big pharma deals that exceeded >$1B in 2022, EV / 2026 revenue was 7.1x. That willingness to pay is one signal that the supply of suitable M&A targets is smaller than appreciated, despite the record # of biotech companies (1/x).
Question:. People predict Big Pharma will go on a spree of acquisitions to replace revenue after loss of exclusivity. * Is that need going up or down? *.
1
5
48
Overview of FDA approved gene, cell and RNA-based therapies. On the gene-editing front, exa-cel ($CRSP / $VRTX) BLA is undergoing rolling review in beta thal and SCD - potential approval in 2023. Source: Piper Sandler
2
8
45
Approval of PD-1/PD-L1 mono and combo therapies in major tumor types. Source: BoA
1
7
42
Potential drugs that could be selected for IRA price negotiations in 2027. The top 20 possibilities (15 will be selected) with data on 2022 CMS Spend, 2026E sales, % Medicare exposure and select competitors that could experience knock-on effects. Additional takeaways:
2
6
44
ADC approvals to date. 12 total approvals (excl. Blenrep which failed a confirmatory study and is requested to be withdrawn) . As a class, ADC peak sales estimated to reach ~$20B by 2026, led by Enhertu, Adcetris and Kadcyla
1
7
45
That's all - If you enjoyed this, follow me @andrewpannu for more biotech charts, musings and breakdowns and consider sharing the below with your audience
Gene therapy landscape. I pulled together 42 public companies and charted the preclinical & clinical assets of each, segmented by approach & vector. Some takeaways:
12
8
40
# of M&A deals by therapeutic area from 2019 - YTD 2022. Oncology has been the most consistent driver, with hematology, CNS and I&I also "hot" areas. Source: JPM
0
8
41
Recent BD activity in the bispecific space. While CD3 remains an important variable domain, there are a growing number of therapies targeting diverse proteins. Multiple deals driven by platform / tech - reflects importance of novel IP & manufacturing flexibility
1
7
40
Overview of clinical-stage gene editing assets. After NTLA-2001 established in vivo clinical PoC, several candidates have emerged for wide range of diseases . On the ex-vivo front, exa-cel ($CRSP / $VRTX) on-track as first gene editing BLA, with potential FDA approval in 2023
1
6
39
M&A and IPO activity in targeted / precision oncology (TO) since 2011. IPOs outpacing M&A - some reasons why:. (1) underperformance of acquired assets vs. consensus.(2) IPOs skewed early, whereas M&A skews late-stage. Result: >40% of TO biotechs are trading near or below cash
2
10
37
Gene editing VC financing (2011 - 2022 YTD) + select deals from 2021-2022. '13-21 CAGR on capital invested: 72.1%.Avg. deal size 2013: $43M.Avg. deal size YTD 2022: $80M . Source: Piper
3
14
37
I think about this differently - it's likely that GLP-1s and traditional NASH drugs like $MDGL's resmetirom co-exist since the underlying opportunity is different. Some obesity drugs like $LLY's retatrutide showed a benefit in NAFLD reduction, which can be thought of as a NASH.
Assuming that GLP1 drugs would evaporate NASH market is grossly underestimating the ability and willingness of people to eat junk food. I am not joking. Those drugs will simply give more room for junk food (metabolic credit) and it will be conveniently used up (like any credit).
3
8
35