EGFRm+ NSCLC Treatment Landscape

Key assets, trials and companies segmented by treatment line and mutation type

Some takeaways from this competitive space:

• This space has been dominated by AstraZeneca's 3rd gen EGFR TKI Tagrisso (osimertinib) due to BIC safety / efficacy profile

Monotherapy Tagrisso is SoC in 1L treatment, and also used in the adjuvant and 2L+ (via combos) settings

Tagrisso generated ~$6B in global LTM sales

• Key past & ongoing trials for AZN that built this blockbuster:
• FLAURA - established Osi mono as 1L SoC (primary value driver)
• FLAURA2 - combines Osi + chemo to further raise the efficacy bar
• ADAURA - looks to establish Osi in adjuvant setting
• While the ADAURA trial showed an OS benefit for Tagrisso, the validity is unclear as there was KOL concern over post-progression treatment in the comparator arm

Only ~39% of control arm patients received Osi upon progression, despite it being SoC for 1L (via FLAURA)

• Looking beyond AZ & Tagrisso, the whole space is set to meaningfully expand:
• JNJ's Rybrevant (ami) is approved in 2L EGFRex20ins NSCLC after chemo (alongside $TAK's Exkivity), but the upcoming MARIPOSA readout (2H'23) will determine usage in 1L setting
• Several 2L+ combos are emerging to displace platinum chemo, including:

(1) Ami + laz + plat chemo (MARIPOSA-2, JNJ)

(2) Osi + plat chemo (COMPEL, AZN)

(3) Teliso-V (ADC) + Osi in MET+ (ABBV)

• Biotechs like MRUS, BPMC and BDTX are looking to establish their assets as potential combo agents with Osi / Ami, in the 2L+ setting, particularly using a biomarker-driven approach such as for MET+ patients. Managing tox is key (vs. maximizing efficacy) to seeing uptick
• Both JNJ and TAK are also looking to displace platinum chemo and move their drugs to 1L in EGFRex20ins NSCLC, along with a host of smaller companies
• For uncommon mutations - Osi (off-label) & BI's afatinib (approved) lead; BPMC & BDTX have early programs to watch
• Safety/tolerability is a huge consideration for emerging treatments

In 1L, mono Osi has an excellent safety profile to pair with ~19mo PFS - the switching cost for docs to Ami (higher tox) may be too high

Even Osi + chemo usage will be limited to manage unnecessary tox

• To get ahead of infusion-related safety concerns & improve convenience for long-duration 1L, JNJ is developing a Sub-Q formulation of Ami with HALO ENHANZE tech

The ongoing PALOMA studies should read out over the next 6-12 months - JNJ has done this before with Darzalex

• While the near-term focus will be on MARIPOSA and 1L commercial dynamics, in the long-term development here will be focused around:

(1) combos of 4th gen EGFR TKIs + established 1L treatments

(2) biomarker-guided approaches

(3) less common mutations